Modeling self-contact forces in the elastic

theory of DNA supercoiling

Cite as: J. Chem. Phys. 107, 3967 (1997); https://doi.org/10.1063/1.474752
Submitted: 17 January 1997 . Accepted: 30 May 1997 . Published Online: 04 June 1998

Timothy P. Westcott, Irwin Tobias, and Wilma K. Olson

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J. Chem. Phys. 107, 3967 (1997); https://doi.org/10.1063/1.474752 107, 3967

© 1997 American Institute of Physics.

Modeling self-contact forces in the elastic theory of DNA supercoiling
Timothy P. Westcott,a) Irwin Tobias, and Wilma K. Olsonb)
Department of Chemistry, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08903
~Received 17 January 1997; accepted 30 May 1997!
A DNA polymer with thousands of base pairs is modeled as an elastic rod with the capability of
treating each base pair independently. Elastic theory is used to develop a model of the double helix
which incorporates intrinsic curvature as well as inhomogeneities in the bending, twisting, and
stretching along the length of the polymer. Inhomogeneities in the elastic constants can also be dealt
with; thus, sequence-dependent structure and deformability can be taken into account. Additionally,
external forces have been included in the formalism, and since these forces can contain a repulsive
force, DNA self-contact can be explicitly treated. Here the repulsive term takes the form of a
modified Debye–Hückel force where screening can be varied to account for the effect of added salt.
The supercoiling of a naturally straight, isotropic rod in 0.1M NaCl is investigated and compared
with earlier treatments of supercoiled DNA modeled by a line of point charges subject to
electrostatic interactions and an elastic potential. © 1997 American Institute of Physics.
@S0021-9606~97!51033-6#

I. INTRODUCTION treatment of supercoiled DNA is to impose a limit on the

distance of closest approach of two chain segments. In this
The elastic theory of rods has been used with recent
approximation, any two points along the DNA curve are re-
success to determine the equilibrium structures of super-
stricted from coming closer than a fixed distance, such as the
coiled DNA.1–8 However, the techniques developed to date
;20 Å diam of the double helix. This hard-sphere limit is
to keep track of the local bending and twisting of chain seg-
easily incorporated in Monte Carlo simulations where one
ments lack a general way to account for the long-range, in-
simply excludes any configuration that violates the distance
tersegmental forces responsible for self-contact. Excluded
constraint.11,20–22 A slightly more sophisticated technique en-
volume effects are, of course, easily incorporated in DNA
tails a Lennard-Jones 6–12 potential,9,12,23,24 the repulsive
models that directly monitor the axis of a chain subject to an
~i.e., van der Waals’! part of which mimics a hard-sphere
assumed potential function,9–16 but that do not necessarily
term. The added London attractions in the 6–12 potential
account correctly for local structural distortions ~because of
lead to the net stabilization of closely contacted chain seg-
computational and/or model limitations!. Most of the pub-
ments, an approximation which is only valid at high ionic
lished work on fully detailed rod models has only considered
strength.25 A third way to deal with self-contact is to intro-
what happens to the DNA up to the point where strand seg-
duce an electrostatic term involving charged residues or seg-
ments, which are distant along the primary sequence, come
ments along the sugar–phosphate chain backbone. The DNA
into close contact as a result of supercoiling. For example,
is reduced in these schemes to an approximate model con-
our recent investigation of protein-anchored DNA loops7 in-
sisting of a point charge per nucleotide residue, each of
cluded contact-free, open states up to the point where the
which is included in the calculation of the electrostatic
DNA strands just begin to touch at a single point. Had those
energy,13 or a sequence of longer segments made up of tens
simulations been continued past this crossed configuration,
of base pairs, which are modeled as interacting charged
the two contacted strands would have simply passed through
rods.26 The effects of the surrounding environment are, re-
each other. The passage event takes place because the only
spectively, treated by decreasing the charge on the phosphate
forces included in the simulation are the local elastic forces
groups to mimic ‘‘counterion condensation’’ 27 or by using a
affecting adjacent DNA segments. The omission of self-
set of salt concentration dependent parameters derived from
contact has, nevertheless, proven useful in treating various
a Poisson–Boltzmann treatment of two infinitely long
aspects of DNA supercoiling, including the onset of writhing
charged cylinders.28 A recent comparison of DNA configu-
in elastic polymers,1,3,17 the twisting and writhing of DNA
rational samples generated with these two electrostatic mod-
circles and loops containing intrinsic bends at low superhe-
els ~counterion condensation versus charged rods! and with a
lical densities,18,19 and the large-scale transitions of DNA
hard-sphere treatment29 has concluded that the charged rod
loops.5–7 Of course, the contact-free approximation limits the
and hard sphere models are better able to account for experi-
types of DNA and supercoiled states that can be considered.
mentally observed salt-induced changes in DNA folding and
Perhaps the simplest way to include self-contact in the
knotting than the counterion condensation scheme. These re-
sults may have been influenced, however, by the simplifica-
a!
Current address: Department of Chemistry & Biochemistry, 0365, Univer- tion of the DNA model to a sequence of 100 Å long charged
sity of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-
segments. Recent enumeration of DNA electrostatics at the
0365.
b!
Author to whom correspondence should be addressed. Electronic mail: level of individual phosphate groups in long circular
olson@rutchem.rutgers.edu chains,30 suggests that an approximate treatment of the poly-

J. Chem. Phys. 107 (10), 8 September 1997 0021-9606/97/107(10)/3967/14/$10.00 © 1997 American Institute of Physics 3967
3968 Westcott, Tobias, and Olson: Self-contact in the elastic theory of supercoiling

electrolyte backbone will underestimate the electrostatic en-

ergy. DNA self-contact has also been treated by identifying
the unknown contact forces that prevent chain intersection
during the course of a finite element analysis of the DNA
elastic rod.4 The procedure is somewhat difficult to imple-
ment since it requires preliminary knowledge of the zones of
contact within the supercoiled molecule. Finally, images of
rods calculated with a computer code that models self-
contact have been recently published,8 but details of the pro-
cedure are not available.
In this paper, we outline a new method to study DNA
supercoiling that produces the fast results of elasticity theory
while also incorporating long-range self-contact forces. We
first derive a system of differential equations that describe
the equilibrium configurations of the self-contacted DNA rod
along the same lines as our earlier treatment of DNA loops.7
We then solve these equations numerically since they are too
complex to be treated analytically. There are three distinct FIG. 1. The local orthonormal coordinate system, (d1 ,d2 ,d3 ), imbedded in
the plane of each base pair. The vectors d1 and d2 span a plane that contains
differences with our earlier work. First, the method devel- the base pair. The vector d1 points in the direction of the major groove and
oped here is able to treat extensibility, which—although it is is parallel to the short axis of the base plane. The vector d2 is orthogonal to
only a second order effect—may be of consequence during d1 and parallel to the long axis of the base plane, pointing in the direction of
protein and drug binding to DNA.31–33 Second, the new the leading strand of the double helix. The vector d3 is perpendicular to the
method includes external forces, thereby allowing the treat- base plane and points along the axis of the DNA double helix in the 5 8 – 3 8
direction of the leading backbone strand. The tangent to the elastic rod is
ment of self-contact via an electrostatic term, a repulsive van coincident with d3 .
der Waals’ term, or both. Finally, here we choose to param-
eterize the DNA rod with Euler symmetric parameters,34 thus
eliminating inherent problems associated with a more tradi-
tional Euler angle representation ~where some angles are in- The local coordinate system (d1 ,d2 ,d3 ) is related to a
determinate under certain computational conditions!. These fixed, orthonormal global coordinate frame (e1 ,e2 ,e3 )
improvements come at a small price. The number of equa- through the 333 transformation matrix T
tions to be solved increases from three to eleven. Neverthe-

less, some of this added complexity is offset by our no
longer having to evaluate computationally expensive trigo-
nometric functions that arise from the use of Euler angles.
II. DESCRIPTION OF THE DNA
Each base pair of the DNA double helix is described by
a local orthonormal coordinate system (d1 ,d2 ,d3 ). The vec-
tors d1 and d2 span a plane that contains the base pair as
shown in Fig. 1. The vector d1 points in the direction of the
major groove and is parallel to the short axis of the base
plane. The vector d2 is orthogonal to d1 and parallel to the
long axis of the base plane, pointing in the direction of the
leading strand of the double helix. The vector d3 is perpen-
dicular to the base pair plane and points along the axis of the
DNA double helix in the 5 8 -3 8 direction of the leading back-
bone strand. The tangent to the central axis of the DNA
double helix is coincident with d3 .
FG FG
d1 e1
d2 5T e2 . ~1!
d3 e3
This matrix can be parameterized by several means, such as
the three Euler angles used in the past to describe a DNA
rod.3,7 Euler angles have the advantage of being efficient by
eliminating redundant parameters, yet they can prove to be
troublesome due to inherent problems associated with the
choice of rotation axes ~e.g., some angles are indeterminate
for certain orientations of the chain in the global coordinate
frame!.
We choose, instead, to use a transformation matrix de-
fined in terms of four so-called Euler symmetric parameters
q 1 ,q 2 ,q 3 ,q 4 , in which case

T5
F q 21 2q 22 2q 23 1q 24

2 ~ q 1 q 2 2q 3 q 4 !

2 ~ q 1 q 3 1q 2 q 4 !
2 ~ q 1 q 2 1q 3 q 4 !

2q 21 1q 22 2q 23 1q 24

2 ~ q 2 q 3 2q 1 q 4 !
2 ~ q 1 q 3 2q 2 q 4 !

2 ~ q 2 q 3 1q 1 q 4 !

2q 21 2q 22 1q 23 1q 24
G . ~2!

J. Chem. Phys., Vol. 107, No. 10, 8 September 1997

 Westcott, Tobias, and Olson: Self-contact in the elastic theory of supercoiling 3969

Since one of the q i is redundant, i.e., there are only three dM

Euler angles, another equation is needed to connect them.
We take the q i to be normalized in the sense that
q 21 1q 22 1q 23 1q 24 51.
Thus defined, the Euler symmetric parameters have two main
computational advantages over the more traditional Euler
angles. First, there are no singularities to avoid during the
calculations, and second, there are no trigonometric func-
tions, which are computationally intensive compared to
simple addition and multiplication. See Ref. 34 for further
mathematical discussion.
If we represent the angular rate of rotation of the local
coordinate frame by k, the rate of change of each of the
coordinate axes with respect to a change in arc length s along
the undeformed DNA curve is
ddi
5 k3di , i51,2,3,
ds
and the rate of rotation written out in terms of its components
is
k5 k 1 d1 1 k 2 d2 1 k 3 d3 ,
where k 1 and k 2 are the curvature components and k 3 is the
twist component.
Substitution of Eqs. ~1!, ~2!, and ~5! into Eq. ~4! yields
2 ~ 11 e ! F3d3 50, ~8!
ds
where M5M 1 d1 1M 2 d2 1M 3 d3 is the resultant internal
~3! moment, d3 is the unit tangent vector as defined above, and e
is the axial extension. In using these equations, all time de-
rivatives are ignored, meaning that, at present, we are only
concerned with the stationary states of the time independent
problem and not with the dynamics.
For the case in which there are no external forces, F is a
constant and Eq. ~8! suffices to describe the equilibrium state
of the DNA. Furthermore, evoking inextensibility ( e 50) re-
duces this one equation to the well known classical
equations35,36 and to the differential equations derived
previously.7 Thus, our use of Eqs. ~7! and ~8!, instead of the
expressions developed previously, has two advantages. First,
we explicitly account for extensibility, which may be impor-
tant when a stretching term is coupled to an untwisting or
~4!
bending term. This coupling is known to occur when a planar
drug or a protein side group intercalates between adjacent
base pairs31–33 or when the DNA is subjected to strong ex-
ternal forces.37 Second, and more importantly, we are able to
~5! include external forces and treat self-contact arising from an
electrostatic term, a repulsive van der Waals’ term, or both.

GF G
the following expression: IV. THE COMPONENTS OF THE MOMENT AND THE

FG F
q 81 AXIAL EXTENSION
k1 q4 q3 2q 2 2q 1
q 82 In order to develop the equations of equilibrium into a
k 2 52 2q 3 q4 q1 2q 2 , ~6!
q 83 form which can be solved numerically, the local components
k3 q2 2q 1 q4 2q 3 q 84 of the moment must be defined. The moments are propor-
tional to the difference between the angular velocity and the
where q 81 , q 82 , q 83 , and q 84 are the derivatives of the Euler intrinsic angular velocity of the DNA spatial pathway
parameters with respect to arc length. We thus have expres-
sions for k 1 , k 2 , and k 3 in terms of the Euler symmetric M 1 5A 1 ~ k 1 2 k 01 ! , ~9!
parameters.
M 2 5A 2 ~ k 2 2 k 02 ! , ~10!

III. THE EQUATIONS OF EQUILIBRIUM
The DNA double helix is modeled as an elastic rod.
Consider two cross sections of the DNA separated by a very
small distance ds. These cross sections make up the ends of
an element of the DNA. The first of two equations that de-
scribe the equilibrium structure of the DNA is obtained by
setting the sum of the forces on each element of the DNA to
zero. Thus,
dF
1f50.
ds
In what follows, the vectors F and f—the resultants of the
internal and external forces, respectively—will be expressed
in terms of their components along the fixed global frame,
i.e., F5F 1 e1 1F 2 e2 1F 3 e3 and f5 f 1 e1 1 f 2 e2 1 f 3 e3 .
The second equation that determines the equilibrium
structure of the DNA is obtained by setting the sum of the
moments on each element to zero. Thus, for a chain free of
external moments
M 3 5C ~ k 3 2 k 03 ! . ~11!
Here, A 1 and A 2 are the bending constants in each of the two
principal directions of bending, C is the twisting constant,
the k i (i51,3) are the deformed angular rates of rotation of
the local coordinate frame, and the k 0i (i51,3) are the in-
trinsic angular rates of rotation. If the DNA chain is treated
at the level of adjacent base pairs, the angular rates of rota-
tion can be related to the tilt, roll, and twist angles measured
in high-resolution atomic structures.38
Also, the axial extension must be defined. This deforma-
~7! tion is taken to be proportional to the component of the re-
sultant of the internal forces in the direction of the tangent
F•d3 5aE e . ~12!
Here, a is the cross-sectional area of the DNA rod, E the
Young’s modulus, and e the relative change in arc length of
the extensible versus the inextensible rod, i.e., (dS
2ds)/ds, where ds and dS are the respective arc lengths
between corresponding slabs in the extensible and inexten-
sible chain.

J. Chem. Phys., Vol. 107, No. 10, 8 September 1997

3970 Westcott, Tobias, and Olson: Self-contact in the elastic theory of supercoiling

V. PARAMETRIZATION OF THE EQUATIONS where the prime denotes the derivative with respect to arc
OF EQUILIBRIUM length.
Before any numerical analyses can be carried out, the Written out in terms of its components in the fixed
equations of equilibrium of the deformed DNA must be ex- frame, Eq. ~7! becomes
pressed in terms of the Euler symmetric parameters detailed h 1 5F 81 1 f 1 50, ~14!
in Eqs. ~2! and ~3!. Furthermore, in order to reduce what
would otherwise be a set of second-order differential equa- h 2 5F 82 1 f 2 50, ~15!
tions to a set first-order differential equations, we introduce
the following four variables, which are the derivatives of the h 3 5F 38 1 f 3 50, ~16!
four Euler symmetric parameters with respect to arc length
and the components of Eq. ~8! along the vectors d1 , d2 , and
Q i [q 8i , i51,2,3,4, ~13! d3 are

h 4 52A 1 ~ q 4 Q 18 1q 3 Q 28 2q 2 Q 38 2q 1 Q 48 ! 14C ~ 2q 3 Q 1 1q 4 Q 2 1q 1 Q 3 2q 2 Q 4 !~ q 2 Q 1 2q 1 Q 2 1q 4 Q 3 2q 3 Q 4 2 21 k 03 !
24A 2 ~ q 2 Q 1 2q 1 Q 2 1q 4 Q 3 2q 3 Q 4 !~ 2q 3 Q 1 1q 4 Q 2 1q 1 Q 3 2q 2 Q 4 2 21 k 02 ! 1 @ 22F 1 ~ q 1 q 2 2q 3 q 4 !
2F 2 ~ 2q 21 1q 22 2q 23 1q 24 ! 22F 3 ~ q 2 q 3 1q 1 q 4 !#@ 112F 1 ~ q 1 q 3 1q 2 q 4 ! /aE

12F 2 ~ q 2 q 3 2q 1 q 4 ! /aE1F 3 ~ 2q 21 2q 22 1q 23 1q 24 ! /aE # 50, ~17!

h 5 52A 2 ~ 2q 3 Q 18 1q 4 Q 28 1q 1 Q 38 2q 2 Q 48 ! 14A 1 ~ q 2 Q 1 2q 1 Q 2 1q 4 Q 3 2q 3 Q 4 !~ q 4 Q 1 1q 3 Q 2 2q 2 Q 3 2q 1 Q 4 2 21 k 01 !
24C ~ q 4 Q 1 1q 3 Q 2 2q 2 Q 3 2q 1 Q 4 !~ q 2 Q 1 2q 1 Q 2 1q 4 Q 3 2q 3 Q 4 2 21 k 03 ! 1 @ F 1 ~ q 21 2q 22 2q 23 1q 24 !
12F 2 ~ q 1 q 2 1q 3 q 4 ! 12F 3 ~ q 1 q 3 2q 2 q 4 !#@ 112F 1 ~ q 1 q 3 1q 2 q 4 ! /aE
12F 2 ~ q 2 q 3 2q 1 q 4 ! /aE1F 3 ~ 2q 21 2q 22 1q 23 1q 24 ! /aE # 50, ~18!

h 6 52C ~ q 2 Q 81 2q 1 Q 82 1q 4 Q 83 2q 3 Q 84 ! 14A 2 ~ q 4 Q 1 1q 3 Q 2 2q 2 Q 3 2q 1 Q 4 !~ 2q 3 Q 1 1q 4 Q 2 1q 1 Q 3 2q 2 Q 4 2 21 k 02 !
24A 1 ~ 2q 3 Q 1 1q 4 Q 2 1q 1 Q 3 2q 2 Q 4 !~ q 4 Q 1 1q 3 Q 2 2q 2 Q 3 2q 1 Q 4 2 21 k 01 ! 50. ~19!

We must also consider the constraints on the Euler sym- cluded in f as a screened Coulombic force, FE i j , defined by a
metric parameters and their derivatives, i.e., Eqs. ~3! and modified Debye–Hückel term between the reduced phos-
~13!. Thus, phate charges of all (i, j) base pair residues, i.e., the phos-
h 7 5q 21 1q 22 1q 23 1q 24 2150, ~20! phate charges are reduced to account for counterion
condensation.27 For convenience, we project all the phos-
h 8 5Q 1 2q 81 50, ~21! phate charge onto the double helical axis and into the plane
of the appropriate base pair. The total electrostatic energy,
h 9 5Q 2 2q 82 50, ~22! E E , is given by a sum of pairwise terms of the form
h 105Q 3 2q 83 50, ~23! d id je 2kri j
h 115Q 4 2q 84 50. ~24!
E E5 (
i, j 4 p e 0e wr i j
, ~25!

These eleven functions (h 1 – h 11) involve eleven unknowns:
the four Euler symmetric parameters (q 1 ,q 2 ,q 3 ,q 4 ), the
four variables introduced as the derivatives of the Euler pa-
rameters with respect to arc length (Q 1 ,Q 2 ,Q 3 ,Q 4 ), and the
global components of the resultant of the internal forces
(F 1 ,F 2 ,F 3 ). Solving these expressions, which are at most
first order differential equations, yields the eleven variables
that describe the equilibrium structure of the DNA.
VI. THE SELF-CONTACT TERM
The external force, f, includes all the long-range interac-
tions that act on a segment of DNA. Electrostatics are in-
where d i is the net charge on the ith base pair. Since there
are two phosphate groups per base pair, d i is 0.48e 2 or
7.7310220 Coulombs assuming 76% phosphate neutraliza-
tion by bound cations in standard B-DNA.27 The distance
between net charges is r i j , e 0 is the permittivity of free
space ~not to be confused with the axial extension, e, which
lacks a subscript!, and e w 577.7 is the dielectric constant of
water at 300 K.39 For solutions of a monovalent salt such as
NaCl, the Debye screening parameter, k ~not to be confused
with the components of the angular velocity, which have
subscripts!, is defined by
k 50.329Ac s Å 21 , ~26!

J. Chem. Phys., Vol. 107, No. 10, 8 September 1997

 Westcott, Tobias, and Olson: Self-contact in the elastic theory of supercoiling 3971

with c s being the molar salt concentration. The screened

Coulombic force between residues i and j is obtained from
the gradient of the appropriate electrostatic energy term

FE i j 5
d id je 2kri j 1
4 p e 0e wr i j r i jS1k
~ r j 2ri !
rij D, ~27!

where (r j 2ri )/r i j is the unit vector between the point

charges. The net electrostatic force is determined for every
pair of charges, so that the external force, fi 5 ( j FE i j , acting
on a phosphate-containing DNA segment is the vector sum
of all the forces of interaction between that residue and all
the other residues.

VII. INCORPORATION OF SELF-CONTACT IN THE

NUMERICAL SOLUTION OF THE EQUILIBRIUM
EQUATIONS
We choose to solve the eleven differential equations in
Eqs. ~14!–~24! numerically. To obtain a numerical solution,
we discretize the elastic rod into a set of n11 nodal points
that are numbered from 0 to n, as shown in Fig. 2. In the
case of closed circular DNA, the first and last nodal points
are identical. The DNA rod also consists of n elements num-
bered 1 to n so that the ith element lies between the
(i21)th and ith nodes. The methods herein are developed in
such a way that the selection of resolution is arbitrary; i.e.,
the ratio between nodes and base pairs is user defined. If one
were to choose the resolution to be one element per base
pair, as we do below, then a base pair would lie at each node.
In deriving Eqs. ~14!–~24! we assumed that the intrinsic
curvatures and the bending and twisting constants do not
vary with arc length. We now translate that constancy into
piecewise constancy of the individual discretized segments.
Thus, if we divide the rod so that one base pair is made up of
at least one segment, then each base pair can have its own
intrinsic curvature, intrinsic twist, and bending, twisting, and FIG. 2. DNA is modeled as an elastic rod which is discretized into a set of
stretching constants. Note that this piecewise constancy is n11 nodal points that are numbered from 0 to n. For the case of closed
circular DNA, the first and last nodal points are identical. The DNA rod also
most appropriate to the study of DNA since the double helix consists of n elements numbered 1 to n so that the ith element lies between
is naturally discretized at the base pair level. the (i21)th and ith nodes.
The eleven variables of functions h 1 to h 11 depend on
the arc length of the DNA rod. Each nodal point has its own
q 1 , q 2 , q 3 , q 4 , Q 1 , Q 2 , Q 3 , Q 4 , F 1 , F 2 , and F 3 . The
parameter j j,i is introduced to designate the jth nodal vari- j j,i 2 j j,i21
j 8j,i 5 , ~28!
ables ( j51,2,3,...,11) at the ith node (i51,2,3,...,n). For l i ~ 11 e i !
example, j 7,100 refers to the value of Q 3 at the 100th node,
and j 11,0 to the value of F 3 at the zeroth node. Because the where l i is the undeformed length of the ith element, and e i
eleven equations of equilibrium are at most first-order equa- is the axial extension of the ith element ~not be confused
tions, only the first derivative of a nodal variable with respect with the permittivity of free space e 0 since there is not a
to arc length needs to be specified. The first derivative of zeroth element!. In terms of the adjacent nodal variables, the
variable j in element i is defined in terms of the difference of axial extension of the ith element is expressed with the use
the nodal variables at consecutive nodes as follows: of Eqs. ~1!, ~2!, and ~12! and the definition of F as

2 j̄ 9,i ~ j̄ 1,i j̄ 3,i 1 j̄ 2,i j̄ 4,i ! 12 j̄ 10,i ~ j̄ 2,i j̄ 3,i 2 j̄ 1,i j̄ 4,i ! 1 j̄ 11,i ~ 2 j̄ 21,i 2 j̄ 22,i 1 j̄ 23,i 1 j̄ 24,i !
e i5 , ~29!
aE

J. Chem. Phys., Vol. 107, No. 10, 8 September 1997

3972 Westcott, Tobias, and Olson: Self-contact in the elastic theory of supercoiling

where j̄ j,i refers to the elemental value of the jth nodal vari-
able and is defined as V5 E 0
L
~ 11 e ! d3 ds. ~32!

j j,i 1 j j,i21
j̄ j,i 5 . ~30! Since, by Eqs. ~1! and ~2!, d3 52(q 1 q 3 1q 2 q 4 )e1 12(q 2 q 3
2
2q 1 q 4 )e2 1(2q 21 2q 22 1q 23 1q 24 )e3 , Eq. ~32! can be rewrit-
The expressions denoted in Eqs. ~28!–~30! can now be ten as the final three equations to be solved
substituted into Eqs. ~14!–~24! to yield eleven equations for
each element, i.e., 11n equations n

H k,i ~ j j,i21 , j j,i ! 50, ~31! P 1 52 ( l i~ 11 e i !~ j̄ 1,i j̄ 3,i 1 j̄ 2,i j̄ 4,i ! 2V 1 50,
i51
~33!

where k51,2,3,...11, and i51,2,3,...n. The problem is thus

n
transformed from one of solving a system of first order, non-
linear differential equations to one of solving a system of P 2 52 ( l i~ 11 e i !~ j̄ 2,i j̄ 3,i 2 j̄ 1,i j̄ 4,i ! 2V 2 50,
i51
~34!
nonlinear algebraic equations. However, there are only 11n
equations for the 11(n11) unknowns. Specifying the n
boundary conditions supplies the required eleven additional
equations. First, the orientation of the first and last residues
P 35 ( l i~ 11 e i !~ 2 j̄ 21,i 2 j̄ 22,i 1 j̄ 23,i 1 j̄ 24,i ! 2V 3 50.
i51
~35!
are known, determining q 1 ,q 2 ,q 3 ,q 4 at both ends of the
DNA. Also, the ends are separated by a given vector V We choose to solve the 11n13 equations using the
5V 1 e1 1V 2 e2 1V 3 e3 . If one end of the rod is located at Newton–Raphson method.40 By applying this approach, we
(0,0,0) T , V is the resultant of the vectorial displacements of obtain a system of equations that take the following matrix
successive chain residues form:

3 434
X1,0 X1,1 0 0 0 0
0 X2,1 X2,2 – – – 0 0 0 Z1
0 0 X3,2 0 0 0 Z2
Z3
– – –
–
– – – –
– – – @ #
Y 5 – ~36!
0 0 0 Xn22,n22 0 0 Zn22
Zn21
0 0 0 – – – Xn21,n22 Xn21,n21 0
Zn
0 0 0 0 Xn,n21 Xn,n ---
------------------------------------------------------ 2P

W0 W1 W2 – – – Wn22 Wn21 Wn

FG
where ] P1
]j j,i
] P2
Wi 5 , ~38!
] H k,i ]j j,i
Xi,l 5 , ~37! ] P3
]j j,i

FG
]j j,i
D j j,1
D j j,2
is an 11311 matrix for j51,2,3,...,11 and k51,2,3,...,11 if
–
lÞ0 and lÞn. At the ends where q 1 ,q 2 ,q 3 ,q 4 are defined Y5 , ~39!
by the boundary conditions, k55,6,7,...,11 and the matrix is –
1137. Note that i runs from 1 to n and that l must be equal –
to either i or i21. Also, D j j,n

J. Chem. Phys., Vol. 107, No. 10, 8 September 1997

 Westcott, Tobias, and Olson: Self-contact in the elastic theory of supercoiling 3973

Zi 52H k,i , ~40! EI 1

U 4 5U 5 5U 6 5 , ~45!
and a

FG
P1 U 7 51.0, ~46!
P5 P 2 . ~41! n
P3 U 8 5U 9 5U 105U 115 , ~47!
L
The (11n13)3(11n13) supermatrix on the left-hand
where L is the contour length of the DNA rod and a is the
side of Eq. ~36! contains all of the partial derivatives of the
cross-sectional area.
equations with respect to each of the nodal variables while
By using input values of the nodal variables, we set up
the (11n13)31 vector to the left of the equal sign in Eq.
and solve the supermatrix in Eq. ~36!, thereby obtaining the
~36! contains all of the corrections to the 11n13 unknown
corrections to the nodal variables. Then, l is chosen as de-
nodal variables. The (11n13)31 vector on the right side of
scribed above and Eq. ~42! can be evaluated to determine the
Eq. ~36! is simply the negative of the algebraic equations
new set of nodal variables. The new values become the input
which we are solving. The matrices Wi , and P are parti-
values and the process is iterated until the Euclidean norm
tioned from other parts of the supermatrix with a dashed line
defined in Eq. ~43! is less than the desired accuracy,
because they arise from the boundary condition that fixes the
131025 , for the calculations that follow.
vectorial displacement of the two ends of the DNA, i.e., Eq.
Note that when we set up the matrix in Eq. ~36!, the
~32!.
external force vector, f, is taken to be independent of changes
Because the components of the matrix in Eq. ~36! lie
in the nodal variables, i.e., the input and output structures at
almost exclusively along the diagonal, the computer solution
each iteration are assumed to be so similar that the external
of the corrections to the Euler symmetric parameters, i.e.,
force of the output structure can be approximated by that of
solving Eq. ~36!, involves the order of N calculations to ex-
the input structure. Otherwise, the (11n13)3(11n13) ma-
ecute. For the methods described above, N is the total num-
trix in Eq. ~36! contains nonzero entries for every entry, and
ber of algebraic equations to be solved in the matrices of Eq.
the computation of the corrections to the Euler symmetric
~36! and is equal to 11n13. However, the calculation of the
parameters would involve an order of N 3 calculations to ex-
external force vector, f, requires the order of N 2 calculations.
ecute, making the study of large DNA prohibitively time
A speed-up technique such as the fast multipole method41
consuming. This estimation of f means that only small steps
could reduce the complexity of the calculation to the order of
can be made in the calculation from one equilibrium struc-
N log N. A tenfold speed-up of the calculation of the elec-
ture to the next. In order that the external force remains
trostatic interactions is expected from such a method for a
approximately constant, the initial and final equilibrium
1000 base pair ~bp! DNA chain.30 In the absence of a
structures must be similar.
speed-up technique, larger DNA chains can be treated at the
base pair level, but the computation time would increase
quadratically with the number of base pairs.
The following Newton–Raphson iteration is carried out VIII. SUPERCOILING PRELIMINARIES

j j,i ~ new! 5 j j,i ~ old! 1lD j j,i , ~42! A. Topology of plasmids

The most important attribute of closed circular DNA is
where l is some number between 0.001 and 1.0, with 1.0
its linking number, Lk, a topological invariant that remains
being the canonical Newton step; that is, 1.0 is the step that
constant under deformation of the double helix. The defor-
would lead directly to the energy minimum if the potential
mation is measured with respect to the intrinsic linking num-
were perfectly quadratic. The resultant of the external forces,
ber, Lk 0 , the linking number of the DNA in its lowest en-
f, is calculated for each iteration. In general, l can be chosen
ergy or relaxed state. The linking number difference, DLk
in many different ways. Here we found that it is best to
5Lk2Lk 0 , is related two other quantities—the writhing
restrict l to the following values: 0.001, 0.01, 0.05, 0.1, 0.5,
number, Wr, and the excess twist, DTw—through White’s
and 1.0. These values are all independently applied in Eq.
formula:42
~42! and l is chosen to be the value that yields the smallest
Euclidean norm of Eqs. ~31! and ~33!–~35! defined as DLk5DTw1Wr. ~48!

A F G
H k,i 2
FG The excess twist, DTw, is the difference between the
2
Li
( 11 n
k51 ( i51 1 ( 3i51 number of times that one of the strands revolves around the
Uk L
norm5 . ~43! central axis of the double helix in a given configuration and
11n13
the number of times that the same strand revolves around the
The U k in this equation are chosen as follows so that the helical axis in the stress-free, intrinsic configuration. It is
norm is expressed in unitless numbers: given by the expression43

U 1 5U 2 5U 3 5
n EI 1
L a
, ~44! DTw5
1
2p
E0
L
~ k 3 2 k 03 ! ds, ~49!

J. Chem. Phys., Vol. 107, No. 10, 8 September 1997

3974 Westcott, Tobias, and Olson: Self-contact in the elastic theory of supercoiling
where k 3 is the component of the angular velocity along the
helical axis as defined previously.
The writhing number, Wr, is a measure of the folding of
the double helix and is determined solely by the spatial tra-
jectory of the DNA axis. It may be defined by the Gauss
double integral43
EE
1 L L ~ t~ s ! 3t~ s 8 !! • ~ r~ s ! 2r~ s 8 !!
Wr5
4p 0 0 u r~ s ! 2r~ s 8 ! u 3
where t, the tangent to the curve, is equivalent to d3 , and r
describes the deformed space curve of the DNA axis.
B. Energy contributions
The bending energy, E B , is defined as
E B5 ES
0
L A1
2
~ k 1 2 k 01 ! 2 1
A2
2 D
~ k 2 2 k 02 ! 2 ds,
where k 1 and k 2 are the components of the curvature in each
of the principal directions, k 01 and k 02 are the components of
the intrinsic curvature in each of the principal directions, and
A 1 and A 2 are the bending constants in each of the principal
directions.
The twisting energy, E T , is given by
E T5 E
0
L C
2
~ k 3 2 k 03 ! 2 ds,
where C is the twisting constant and k 03 is the intrinsic twist
density.
The stretching energy, E S , is defined by
E L Ea 2
E S5 e ds,
0 2
where E is the Young’s modulus, a is the cross-sectional
area of the DNA rod, and e is the extension. This term ig-
nores the explicit coupling between twist and stretch ob-
served in DNA crystal structures31–33 and recently deduced
from physical measurements.44,45
The screened Coulombic energy, E E , is calculated be-
tween all pairs of charges using the Debye–Hückel formula
given by Eq. ~25!.
C. Elastic and electrostatic constants
The elastic and electrostatic constants used in the com-
putations are based on observed physical properties of DNA.
The constants associated with the bending and twisting of
DNA are obtained from the persistence length, P, of DNA.
For an isotropic, intrinsically straight rod, the persistence
length is equal to the unique bending constant, A, divided by
kT. 46 Since the nonelectrostatic contribution to the persis-
tence length is ;310 Å, 47 A5A 1 5A 2 51.3310219 erg cm
at 300 K. If the DNA is modeled as a rod with a circular
cross section of radius 10 Å, the cross-sectional area is
3.1310214 cm2, and the principal moments of inertia, I 1 and
I 2 are 7.9310229 cm4, a number equal to p /4 times the
radius to the fourth power. Also, since A 1 [EI 1 , Young’s
J. Chem. Phys., Vol. 107, No. 10, 8 September 1997
TABLE I. Values, in cgs units, for the physical constants used to model an
ideal intrinsically straight DNA rod at a given monovalent salt concentration
using Eqs. ~25! and ~48!–~53!.
Quantity Symbol Value
Bending constant A,A 1 ,A 2 1.3310219 erg cm
Twisting constant C 1.0310219 erg cm
Intrinsic bend k 01 , k 02 0 cm21
dsds 8 , Intrinsic twist rate k 03 1.83107 cm21
Young’s modulus E 1.63109 dyne/cm2
~50! Cross-sectional area a 3.1310214 cm2
Intrinsic length per base pair l 0
3.431028 cm
modulus, E, is calculated to be 1.63109 dyne/cm2. The ratio
between the bending and twisting constants, A/C, is as-
sumed to be 1.25. We thus take C51.0310219 erg cm for
~51!
the twisting constant, a number lower than recently measured
values in typical linear and large circular plasmids
(;2310219 erg cm). 48
For naturally straight B-DNA, the intrinsic curvature is
zero ~i.e., k 01 5 k 02 50!, and the intrinsic separation of succes-
sive base pairs is equal to the helical step height, l 0
53.431028 cm. Since the intrinsic curvature is zero and
both bending constants are identical, we can take advantage
of the fact that the twist rate, k 3 , and intrinsic twist rate, k 03 ,
~52!
do not need to be known specifically. Only the excess twist
density, k 3 2 k 03 , is relevant. For the computer simulations
that follow, we will assume that a 1000 bp chain in its in-
trinsic naturally straight state has a twist, Tw, of 96. This
choice yields a twist rate, k 3 , of 96•2 p /(3400 Å)
50.18 Å 21 51.83107 cm21, corresponding to 1000/96
510.4 base pairs per turn of the double helix, a value con-
~53! sistent with the observed helical twist of random sequence
DNA.49 The physical constants necessary for calculation of
the quantities in Eqs. ~48!–~53! are summarized in Table I.
IX. THE SUPERCOILING OF DNA IN 0.1 M NaCl
We start by modeling a 1000 bp DNA as an isotropic,
intrinsically straight, inextensible rod. The chain so modeled
can be compared with previous studies of supercoiled DNA
which do not consider the extensible nature of the DNA
molecule.11,12,20,24,50 The linking number difference, DLk, is
gradually decreased from a value of 0 to a value of 26,
corresponding to a superhelical density of 26/96520.06
which is comparable to values that exist naturally in the
cell.51
We study the equilibrium structures obtained when the
molar monovalent salt concentration is 0.1. Selected equilib-
rium structures are shown in Fig. 3. When the linking num-
ber difference, DLk, is zero, the DNA is found to adopt the
expected circular form. As the linking number difference is
decreased, the polymer undergoes a configurational change,
first into a figure-eight with one point of close approach and
later into various interwound forms. When DLk526, the
equilibrium configuration of the DNA is highly interwound
and writhed, i.e., the writhing number, Wr, is decreased
from the value of zero characteristic of the circular state to a
 Westcott, Tobias, and Olson: Self-contact in the elastic theory of supercoiling
FIG. 3. Selected equilibria for an inextensible 1000 bp DNA in 0.1M salt at DLk50,22,24,26. The increase in shading intensity reflects the increasing
magnitude of twist density.
value of 24.1, indicative of about four negative crossings of
the chain axis observed in all possible views of the DNA.
It is important to note that the structures shown in Fig. 3
are mechanical equilibria since we are only solving the time
independent equations of elasticity. The DNA strands, which
are several persistence lengths long, will not remain in these
static configurations, but instead will fluctuate around these
minimum energy shapes. Whereas the Wr of the most highly
interwound DNA in Fig. 3 is not necessarily 24.1 at any
particular point in time, it is expected to fluctuate about that
value. The extent to which the DNA does fluctuate about the
equilibrium structure will be the subject of future research.
The strategy employed here is to identify as many local
minima as possible for a DNA with a given linking number
deficit and to compare the energy differences among those
minima to kT.
The change in global shape can be followed quantita-
tively by plotting Wr as a function of DLk as is done in Fig.
4~a!. The plot in Fig. 4~a! is divided into two parts, the circle
branch and the interwound branch. The circle branch corre-
sponds to the set of equilibrium structures that are obtained
by starting from a circle with DLk50 and slowly lowering
the value of DLk. The branch is followed until Wr becomes
less than 20.01, at which point large changes in the writhing
number occur; thus, the structures along the circle branch are
circles with Wr'0 and DLk'DTw. The interwound branch
is the set of equilibrium structures that are obtained by start-
ing from a figure-eight with DLk521 and slowly decreas-
ing the value of DLk. This branch is followed until the link-
ing number difference reaches 26.
Since there is more than one equilibrium structure for
each value of DLk, we must compare the total energies of
J. Chem. Phys., Vol. 107, No. 10, 8 September 1997
3975
the circle and interwound structures at a given DLk. The
structure with the lower total energy will be the more fa-
vored configuration. The total energy for the circle and in-
terwound branches is plotted as a function of DLk in Fig.
4~b!. For each branch, the total energy increases in a qua-
dratic manner with decreasing DLk. Furthermore, when the
linking number difference is greater than 21.7, the circle is
lower in energy, and at a lesser DLk, the interwound branch
is lower in energy. Note that the electrostatic energy for the
circle branch in Fig. 4~b! is constant, whereas that for the
interwound branch remains relatively constant with decrease
in DLk until a value of approximately 23.5, at which point
the electrostatic energy shows a different dependence on
DLk. This value of DLk corresponds to the transition from a
figure-eight equilibrium configuration where there is only on
point of self-contact into a true interwound form where there
is a region of self-contact. The same change in slope near
DLk523.5 can be seen in the total energy as well as in the
writhing number in Fig. 4~a!.
The bending and twisting components of the elastic en-
ergy are plotted as a function of the linking number differ-
ence in Fig. 4~c!. As expected, the bending energy of the
circle remains constant and the twisting energy increases
quadratically. The elastic energies of the interwound forms
are more interesting. Again, a transition can be seen near
DLk523.5. The bending energy remains relatively constant
until this transition point is reached, after which it increases
linearly. This follows from the roughly constant shape of the
figure-eight found at values of DLk,23.5 and the changing
shape of the interwound form with further decrease in DLk
~see below!. Also, the twisting energy increases steadily up
to DLk523.3, at which point it begins to decrease slightly.
3976 Westcott, Tobias, and Olson: Self-contact in the elastic theory of supercoiling
FIG. 4. Writhing number and energy terms of equilibrium states of an
inextensible, intrinsically straight, isotropic 1000 bp DNA in 0.1M salt: ~a!
writhing number, Wr; ~b! total energy, E, and screened Coulombic energy,
E E ; ~c! bending energy, E B , and twisting energy, E T .
J. Chem. Phys., Vol. 107, No. 10, 8 September 1997
The writhing numbers that we obtain for a given DLk
and salt concentration are consistently larger than those ob-
tained by Schlick et al.26 who use a Debye–Hückel model of
interacting rods rather than explicitly evaluate pairwise
terms. More specifically, at DLk526 and 0.1M salt, we
calculate Wr524.1, whereas Schlick et al. find Wr52.2
when DLk56. The difference in sign of Wr and DLk simply
reflects a different choice of handedness of the superhelix:
for purposes of comparison only the absolute value of the
writing number is significant. The differences in u Wr u in the
two simulations are most likely due to the different methods
used to treat the electrostatic interactions, but may also re-
flect the representation of the DNA axis by a sequence of
cubic B-spline curves rather than as an elastic rod. The ab-
solute values of Wr in both studies, however, are smaller
than those obtained under corresponding conditions with a
hard-sphere or van der Waals’ term consistent with the
;20 Å diam of the double helix.11,12,20,24,50
X. THE CONTACT ZONE
The interwound configurations of supercoiled DNA con-
tain a central region where parts of the DNA come into self-
contact. In order to learn more about this structural feature,
the closest approach of DNA segments separated by at least
60 bps along the DNA contour was calculated over the range
of DLk studied. The results, which are displayed in Fig. 5~a!,
show that while the magnitude of DLk is small, the DNA
remains in the figure-eight configuration with a single point
of close contact and a single minimum of close approach on
the contour surface. However, at DLk523.75 the appear-
ance of the surface changes, reflecting a transition from a
structure with single point of minimal approach to one in
which two more sets of chain segments are a similar distance
apart. Interestingly, this value of DLk is slightly lower than
the value of DLk523.5 deduced from the transitions in the
writhing number and energy plots. Furthermore, for the true
interwound structures there is a region of self-contact over
which the distance of closest approach varies within the con-
tact zone.
A closer look at the contact region is shown in Fig. 5~b!
for integral linking number differences. As the DLk de-
creases from 21 to 26, nonbonded segments of the DNA
come into increasingly closer approach with the absolute
minimum decreasing from 118.8 to 41.7 Å, see Table II. The
different character of close approach with change in DLk
and contour point differs from the fixed nonbonded distances
assumed in hard sphere, van der Waals’, and simplified elec-
trostatic models of nonbonded contact,26 where the distance
between chain segments in the Debye–Hückel model of in-
teracting charged rods is taken as 56 Å. Also note that the
equilibrium structure found at DLk523 has a point of con-
tact that is closer than any point of contact in the interwound
DLk524 structure. The DLk521, 22, and 23 configu-
rations are figure-eights with a single minimum of close ap-
proach, whereas the other three structures are true inter-
wound forms with an extended zone of close contacts. All of
the figure-eights are characterized by a writhing number
 Westcott, Tobias, and Olson: Self-contact in the elastic theory of supercoiling 3977

FIG. 5. ~a! The distance of closest approach between a given residue and another base pair that is at least 60 bps distant along the DNA axis. ~b! A closer look
at the contact region for integral linking number differences.

J. Chem. Phys., Vol. 107, No. 10, 8 September 1997

3978 Westcott, Tobias, and Olson: Self-contact in the elastic theory of supercoiling
TABLE II. Distance of closest approach, d, of any two base pairs that are
separated by at least 60 bps along the DNA axis. The value of d is shown
for the integral DLk structures.
DLk d ~Å!
21 118.8
22 55.6
23 47.9
24 50.0
25 43.8
26 41.7
within 0.2 of 21, indicating that they adopt structures of
generally similar appearance; however, the distance between
segments that form the single point of contact can vary over
a wide range. Thus, not all figure-eights are alike; those with
a higher degree of supercoiling have a smaller distance of
closest approach than those with a lower degree of supercoil-
ing. The figure-eight branch can be roughly classified into
two separate parts. In the first, between DLk521 and 21.9,
the distance of closest approach rapidly decreases, while the
two lobes change very little. In the second, beyond DLk5
22, the distance of closest approach varies much more
slowly, and the two lobes begin to rotate with respect to each
other. It is the figure-eight at the interface between the two
subclasses of figure-eights that most closely resembles the
ideal planar form.
The nonbonded distances in the central contact zone of
the interwound structures are not uniform, but rather exhibit
a roughly sinusoidal variation with chain contour. The num-
ber of distance maxima within the contact region increases in
a one-to-one correspondence with the magnitude of DLk.
For example, the DLk524 structure has a single distance
maximum, the DLk525 structure two distance maxima,
and the DLk526 structure three distance maxima. While
the number of periods in the variation of distance increases,
the amplitude decreases from 10.2 Å to 8.3 Å to 5.7 Å for
the DLk524, 25, and 26 structures, respectively. Note
also that there are two absolute distance minima for each
interwound structure, and they are located at the ends of the
contact zone. Finally, the closest approach of DNA segments
occurs at the start and finish of the contact region, not in the
middle.
XI. EFFECTS OF EXTENSIBILITY
In order to determine the effects of extensibility, we
have computed equilibrium structures of an extensible, in-
trinsically straight, 1000 bp DNA in 0.1M salt over the same
range of DLk considered above for the inextensible model.
As evident from Fig. 6~a!, the variation of writhing number
with DLk for these extensible structures is very similar to its
inextensible counterpart in Fig. 4~a!. The greatest difference
in writhing number occurs at DLk526 where Wr524.0
compared to 24.1 for the inextensible model at the same
point.
Small differences are evident in the total and electro-
static energies @compare Fig. 6~b! to Fig. 4~b!#. First note the
J. Chem. Phys., Vol. 107, No. 10, 8 September 1997
lower magnitude of the electrostatic energy for the extensible
circular form compared to the inextensible chain, yielding
smaller total energies. Even though the DNA configurations
have exactly the same shape in each case, the extensible
DNA stretches to provide a greater distance between the
charged residues along the DNA chain. The stretching, how-
ever, has no effect on the crossover in energy between the
circle and interwound branches, which again occurs at a link-
ing number difference of 21.7. The total energy for the ex-
tensible interwound branch also splits into two distinct re-
gions: before and after DLk523.5. These two regions
correspond to the figure-eight form where there is only a
single point of self-contact and the true interwound forms
where there is a region of self-contact.
The greater difference in magnitudes of the electrostatic
and total energies in the extensible DNA stems from the
stretching energy shown in Fig. 6~c!. In our original compu-
tations, there was no DNA extension and the stretching en-
ergy was zero, but for the extensible case, the stretching
energy remains constant at about 11 kT for all structural
forms. The DNA expands from an intrinsic length of 3.4 Å to
an equilibrium length of 3.48 Å per base pair. Since the
stretching is essentially independent of global configuration,
we infer that it arises from the repulsion of adjacent charges
along the primary sequence, rather than from features of a
specific configuration.
XII. CONCLUDING REMARKS
A system of eleven differential equations that describe
the equilibrium structure of DNA is derived. This new for-
malism has three advantages over a similar set of equations
derived previously.7 First, and most importantly, the new
methods provide a mechanism for treating the long-range
self-contact which is characteristic of supercoiled DNA. Sec-
ond, the approach also allows for the treatment of extensibil-
ity. Finally, the Euler symmetric parameters used to describe
the configuration of the DNA in space avoid an inherent
singularity associated with the Euler angles used previously.
While the set of eleven differential equations introduced here
may seem more computationally complex than the three
equations derived previously, the added complexity is offset
by our no longer having to evaluate the computationally ex-
pensive trigonometric functions that arise from the use of
Euler angles. The numerical methods further allow for the
treatment of DNA chains that are thousands of base pairs
long. Moreover, each base pair can have its own bending,
twisting, and stretching stiffnesses and its own intrinsic
bending and twisting angles; thus, base sequence effects can
be studied.
The computed structures of a 1000 bp DNA modeled as
an isotropic, intrinsically straight, inextensible rod at 0.1M
NaCl are qualitatively similar to those obtained previously
with similar chain models.11,12,20,24,50 The equilibrium struc-
tures found at a given writhing number, however, are more
highly writhed than those identified with a Debye–Hückel
model of interacting rods at the same salt concentration.26
The incorporation of DNA extensibility yields similar results
 Westcott, Tobias, and Olson: Self-contact in the elastic theory of supercoiling 3979

with only minor differences in the electrostatic, stretching,

and total energies. Finally, detailed analysis of intramolecu-
lar contacts reveals that the zone of nonbonded interactions
found in true interwound configurations not only increases in
size with increasing DLk but also changes in character, with
states of higher DLk coming into increasingly closer ap-
proach. Furthermore, intersegmental distances are not uni-
form along the contact zone of interwound structures as is
frequently assumed.
While the methods developed here allow for the treat-
ment of DNA as a heteropolymer, the present application
assumes that the chain is intrinsically straight with uniform
elastic constants. This approximation is made in order to
check the current approach against earlier simulations of the
same model obtained with different computational ap-
proaches. While the earlier studies also incorporate self-
contact and extension, none can yet treat base sequence-
dependent inhomogeneities in the DNA. The study of
uniform, naturally straight double helical models has pro-
vided considerable insight in the past into the overall prop-
erties of long stretches of DNA devoid of intrinsic structure
or deformability. As will be demonstrated in detail else-
where, the preferred configurations of supercoiled DNAs
with realistic chemical features are strikingly different from
those of homogeneous, naturally straight rods. For example,
intrinsically curved DNA fragments not only adopt three-
dimensional arrangements different from chains that obey
the isotropic rod model, but also show pronounced variations
in the local twist of successive base pairs.52,53

ACKNOWLEDGMENTS
The authors would like to thank Dr. Marcia O. Fenley
for valuable comments and Mr. Andrew J. Olson for assis-
tance with molecular graphics. This research has been
funded by the U.S. Public Health Service under grant
GM34809. T.P.W. was a predoctoral trainee supported in
part by a grant from the U.S. Public Health Service ~Molecu-
lar Biophysics Training Grant GM08319! and by the Depart-
ment of Education ~National Needs in Chemistry Program!.

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J. Chem. Phys., Vol. 107, No. 10, 8 September 1997