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Internal Coordinate Density of State from

Molecular Dynamics Simulation
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Impact Factor: 3.6 DOI: 10.1002/jcc.23822

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Internal Coordinate Density of State from Molecular

Dynamics Simulation
Pin-Kuang Lai and Shiang-Tai Lin*
The vibrational density of states (DoS), calculated from the
Fourier transform of the velocity autocorrelation function,
provides profound information regarding the structure and
dynamic behavior of a system. However, it is often difficult
to identify the exact vibrational mode associated with a specific frequency if the DoS is determined based on velocities
in Cartesian coordinates. Here, the DoS is determined based
on velocities in internal coordinates, calculated from Cartesian atomic velocities using a generalized Wilsons B-matrix.
The DoS in internal coordinates allows for the correct detec-

tion of free dihedral rotations that may be mistaken as hindered rotation in Cartesian DoS. Furthermore, the
pronounced enhancement of low frequency modes in Cartesian DoS for macromolecules should be attributed to the
coupling of dihedral and angle motions. The internal DoS,
thus deconvolutes the internal motions and provides fruitful
C 2015 Wiley
insights to the dynamic behaviors of a system. V
Periodicals, Inc.

Introduction

specific frequency (eigenvectors of the Hessian matrix) is lost

in the DoS calculations.
One possible way to reconstruct the link between the direction of atomic motion and the DoS is to determine the velocity spectrum using the internal coordinates, which could be
different from that using the Cartesian coordinates. For example, when a rigid rotor rotates at a constant angular velocity
x, the velocity spectral density is a delta function at frequency
x/2p based on linear velocity (v 5 xd/2sin(xt) with d being
the length of the rigid rod), whereas it is a delta function at
zero frequency based on angular velocity. Note that in the
limit where the mode becomes harmonic (e.g., rigid rotors in
the solid state at low temperatures), the DoS calculated from
different coordinate systems are identical.
Classical molecular dynamics simulations that integrates the
Newtons equations of motion based on internal coordinates
have been proposed.[1820] Unfortunately, such simulations are
often less efficient compared to those based on Cartesian
coordinates because reduced mass associated with each internal mode can be time dependent (especially for flexible molecules). The recalculation of the reduced mass significantly
increases the computational cost. Therefore, most popular
molecular simulation packages[2124] perform integration of
equations of motion in the Cartesian coordinates. Therefore, it
is desirable to have a robust approach to obtain the DoS in
internal coordinates from molecular dynamics simulation (MD)
performed in Cartesian coordinates.

The normal modes, or vibrational density of states (DoS), provides profound insights to the structure details,[1,2] dynamic
behaviors,[3,4] and thermodynamic properties[58] of a system.
Some experimental methods include infrared and Raman scattering are often used to obtain vibration DoS.[2,9] The normal
modes are a way of representing the dynamics of atoms in a
system using a collection of independent oscillatory motions.
At low enough temperatures, the system is trapped in the
quadratic (harmonic) potential surface near some energy minimum, and the normal modes can be calculated from the curvatures of the potential surface, that is, the Hessian matrix (the
second derivative of the potential energy with respect to
atomic positions at equilibrium geometry).[1012] The square
root of the eigenvalues of the Hessian matrix are the frequency of the normal modes, and the corresponding eigenvectors provide the direction of atomic movements associated
with each mode.
As the temperature increases, the potential surface may no
longer be harmonic and the Hessian matrix calculations can
become inadequate. Under such circumstances, effective normal modes can still be determined from the covariance of
atomic position fluctuations under the quasiharmonic approximations.[13,14] Some efforts were made to include an harmonic
effects in such analysis.[15,16]
Another representation of dynamic of a system using an
effective harmonic vibration is the power spectral density of
the mass-weighted velocity, or the DoS.[17] In this case, the
dynamic behavior of each atomic motion is represented by
supposition of sinusoidal oscillations using the Fourier series.
Therefore, the velocity spectral density indicates the distribution of the vibration in the frequency domain. Note that the
DoS agrees with the normal modes (eigenvalues) determined
from the Hessian matrix for harmonic systems. However, the
collective motion of atoms (eigenvectors) associated with a

DOI: 10.1002/jcc.23822

P.-K. Lai, S.-T. Lin

Department of Chemical Engineering, National Taiwan University, Taipei
10617, Taiwan
E-mail: stlin@ntu.edu.tw
Contract grant sponsor: National Science Council of Taiwan; Contract
grant number: NSC 1012628-E-002014-MY3
C 2015 Wiley Periodicals, Inc.
V

Journal of Computational Chemistry 2015, DOI: 10.1002/jcc.23822

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Despite of its importance, the transformation of atomic

velocity in Cartesian coordinates to velocities in internal coordinates is nontrivial. Unlike the normal modes, the internal
coordinates are not orthogonal to each other[25] and overcomplete (i.e., internal coordinates that can be defined are
greater than the degree of freedom). The most well-known
approach is the Wilsons method,[26,27] where a 3N 3 3N Bmatrix is constructed to convert Cartesian displacements of
all N atoms in a system to internal displacements. Recently,
van Houteghem et al.[28] proposed a velocity projection
method to obtain bond-stretching velocities by considering
contributions of Cartesian atomic velocities parallel to the
bond direction. However, the extension of the method to
other types of internal modes has not been demonstrated. In
this work, we applied the Wilsons method to convert velocity
in different coordinate systems through the B-matrix. The
advantage of this method is that all internal modes can be
obtained simultaneously and the complete DoS from internal
velocity can be constructed. We validated, thus determined
internal velocities using numerical differentiation of displacement in internal coordinates, and compared the differences
of DoS determined from velocity in different coordinates. Our
results show that the internal DoS has many advantages and
provides more physical insights compared to Cartesian DoS
alone.

The vibrational DoS

The vibrational DoS, or velocity spectrum of a component, is
defined as the mass-weighted sum of velocity spectral density
from all atoms in the system,[17]
2 XNk X3
m sb t
j51
b51 j j
kT

(1)

where mj is the mass of atom j. Nk is the total number of

atoms of molecule k. The velocity spectral density sbj t of
atom j in the bth coordinate (b 5 x, y, and z in the Cartesian
coordinate) is determined from the square of the Fourier transform of the velocities as

2
1  s b

b
sj t5 lim
vj te2i2ptt dt 

s!1 2s 2s

(2)

The DoS can be also calculated from the Fourier transform of

the velocity autocorrelation function.[17] The integration of St
gives the total degrees of freedom of the system.
1
St53N

(3)

Cartesian vibrational velocity

For polyatomic species, the velocity of an atom j contained in
a molecule k at a time instant t can be decomposed into
translational, rotational, and vibrational velocities.[6]
2

(4)

The translational velocity (vj,trn) is set to be the center of

mass velocity of the molecule
X
v j;trn 5

mi v
X i;tot
mi

(5)

where the summations run over all atoms contained in molecule k. The angular velocity (x) is determined from the angular
momentum (L) and the inverse of principle moments of inertia
tensor (I )
L5

mj r j 3v j;tot 5I x

(6)

where r j is the position vector of atom j to the center of mass

of the molecule. The rotational velocity is then obtained from
v j;rot 5x3r j

(7)

and the vibrational velocity is obtained from

v j;vib 5v j;tot 2v j;trn 2v j;rot

(8)

Internal vibrational velocity from Wilsons method

Methods and Theory

St5

v j;tot t5v j;trn t1v j;rot t1v j;vib t

Journal of Computational Chemistry 2015, DOI: 10.1002/jcc.23822

The vibrational velocity obtained from eq. (8) are the atomic
velocity with the center of mass translation and rotation contributions removed. Here, we would like to express the intramolecular vibrations (vj,vib) in terms of contributions from
bond stretching, angle bending, dihedral torsion, and so forth.
The conversion from Cartesian velocity to internal velocity can
be achieved by Wilsons B-matrix.[26,27] Assuming infinitesimal
amplitudes of vibration, the atomic displacement in Cartesian
coordinates (Dx) can be converted to those in the in internal
coordinates (Dq)[26]
Dq5B Dx

(9)

where B is a 3Nk 3 3Nk matrix (Nk is the number of atoms in

molecule k) whose elements are the change in internal coordinates corresponding to an infinitesimal perturbation in Cartesian coordinates, that is,
Bab 5

@qa
@xb

(10)

Note that b denotes any one of the 3Nk degrees of freedom

in Cartesian coordinates (x, y, or z directions), and a denotes
any one of bonds, angles, and dihedrals degrees of freedoms
in internal coordinates (q). The analytical form of elements in
B , that is, Bab, is fairly complicated, especially for dihedral torsion, which requires tedious algebra[29] and may become formidable for large molecules. In this work, Bab are determined
from numerical differentiation in terms of the change in internal coordinates with respect to perturbation in Cartesian
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Figure 1. Schematic representation of bond (B), angle (A), and torsion (T).

coordinates (see Appendix for detail). Once the B matrix is

_ can be
available, the velocity in the internal coordinates (q)
calculated as[30]
_
x_
q5B

(11)

where the velocity x_ in Cartesian coordinates is equivalent to

v vib obtained from velocity decomposition of the MD trajectory. Equation (11) follows from the time derivative of eq. (9),
assuming B is constant over an infinitesimal time interval. The
validity of this assumption is examined using numerical derivative of displacements in internal coordinates described in the
next section.
Internal vibrational velocity from numerical method
In the Wilsons method, the internal velocities are determined
from eq. (11). It is also possible to determine the internal velocities directly without resorting to Cartesian velocities. This can be
achieved by calculating the time derivatives of bonds, angles,
and dihedral torsions from the trajectory of a MD simulation.
The definition of bond Bj (in length), angle Aj (in radian), and torsion Tj (in radian) are illustrated in Figure 1 and are calculated as
Bj 5jjb j jj5jjr j11 2r j jj
Aj 5cos 21

Tj 5cos 21

(12)

 b b 
j21
j

(13)

jjb j21 jjjjb j jj

b j22 3b j21  b j21 3b j

jjb j22 3b j21 jjjjb j21 3b j jj

angles, and Nk 2 3 dihedrals. However, it is often the case that

many more internal modes can be defined (overcompleteness).
For example, ethane (Nk 5 8) contains seven bonds (six CH and
one CC), 12 angles (six HCH and six HCC), and nine dihedrals
(nine HCCH), although there should only be six unique angles
and five unique dihedrals. Note that the energy change associated with the displacement of each of these 28 internal modes
(force field parameters) needs to be specified in a MD simulation. In the original Wilsons method, one needs to select the
unique angles and dihedrals (and the center of mass translation and rotation) to form a square matrix B [eq. (10)]. This is
necessary if one were to evaluate the G-matrix where the
inverse of B is required. However, all (more than 3Nk 2 6
modes) internal modes can be included in the B-matrix, and
the velocity associated with each mode can be obtained. We
have included all the internal modes in the calculation of Bmatrix in this work and rescaled their contributions to the
overall internal DoS, that is,
"
#
NB
NA
ND
2 X
sa t Nk 21 X
sa t Nk 22 X
sa t Nk 23
SIntvib t5
1
1
k a51 Ta NB
Ta NA
Ta ND
a51
a51
(18)
where Ta is the temperature of an internal mode a, and NB,
NA, and ND are the number of bonds, angles, and dihedrals,
respectively. The scaling of DoS is due to overcompleteness of
internal modes. This scaling ensures that the DoS integration
would be equal to internal degree of freedom [eq. (3)]. The
DoS of each internal mode is defined as

2
1  s p

Ia q_ a te2i2ptt dt 

s!1 2s 2s

sa t5 lim

(19)

where Ia is the reduced mass associated with internal mode a.

For a dynamic system, Ia is time and structure dependent.
Note that integrating eq. (19) over frequency and applying
Parsevals theorem gives
1

(14)

1
1
sa tdt5 hIa q_ 2a i5 kTa
2
2

(20)

The velocity of each mode is obtained from numerical differentiation as follows

Bj t1s2Bj t
B_ j t10:5s5
s

(15)

Aj t1s2Aj t
A_ j t10:5s5
s

(16)

Tj t1s2Tj t
T_ j t10:5s5
s

(17)

where a time interval s 5 4 fs is used in our study.

DoS from velocity in internal coordinates
In Wilsons method, the 3Nk 2 6 internal degrees of freedom
(or 3Nk 2 5 for linear molecule) consists Nk 2 1 bonds, Nk 2 2

In the next section, we discuss the evaluation of the

reduced mass.
Mass of internal mode
The mass associated with each internal mode is needed for
the evaluation of kinetic energy and temperature associated
with the mode. Mass and temperature are also important for
the calculation of thermodynamic properties from the DoS.[58]
The reduced mass for bond and angle can be determined analytically for diatomic and some triatomic molecules.[31,32] However, there is no analytical expression for the reduced mass of
dihedral torsion, and various approximations[33] were proposed
for this purpose. In this work, we propose a new, simple
method for Ia from the mass of atoms associated with the
internal mode a.
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mj12 mj11
jjr j12;j11 jjsin Aj11 2
mj12 1mj11
!
r j12;j11  r j12;j11
21
Aj11 5cos
jjr j12;j11 jjjjr j12;j11 jj

lj12 5

(28)

(29)

The accuracy of this method is tested from corresponding

temperature of each mode by equipartition theorem. The temperature associated with an internal mode a can be calculated
as
Ta 5

Figure 2. Schematic representation for calculation of the reduced mass for

bond (a), angle (b), and dihedral torsion (c).

The reduced mass for bond that belongs

to atoms j and j 1 1 (Fig. 2a) can be determined exactly as

Bond-reduced mass.

Ibond 5

mj mj11
mj 1mj11

(21)

Angle-reduced mass. The harmonic motion of angle bending

is considered as the stretching of two reduced bonds (the two

squares in Fig. 2b). The reduced mass for angle that belongs
to atom j 2 1, j, and j 1 1 is
lj21 lj11
lj21 1lj11

(22)

lj21 5

mj21 mj
jjr
jj2
mj21 1mj j21;j

(23)

lj11 5

mj11 mj
jjr
jj2
mj11 1mj j11;j

(24)

Iangle 5
where

(30)

where hIa q_ 2a i is twice the kinetic energy associated with internal mode a, and the angle brackets denotes < > ensemble
average. For a thermally equilibrated system (i.e., equipartition[34,35] is satisfied), the temperature determined from any
degrees of freedom of the system is the same as the system
temperature T. Therefore, the ratio of Ta and T is thus an indication of appropriateness of the proposed internal mass.
ca 5

T
Ta

(31)

As the reduced mass proposed in eqs. (21), (22), and (25)

assumes no coupling between different internal modes, the
deviation of ca should be close to unity for small molecules
and may deviate from unity for large molecules where coupling of reduced mass become important.
However, it is noted that although temperature is related
with mass, their values cancel out for total internal DoS in eq.
(18). In other words, the performance of DoS is irrelevant of
mass, but as stated earlier, accurate mass and temperature are
important for subsequent analysis using DoS.
Note that the Wilsons method also provides an equivalent
mass calculation in a matrix form. This mass matrix has been
used in an internal coordinate molecular dynamics as well.[18]
This is obtained from the fact that the kinetic energy (EK) is
independent of coordinate system, that is,

Torsion-reduced mass. From Newman projection, the dihedral

_ q_ T G -1 q_
_ q_ T B -1 T M B -1 q5
2EK 5x_ T M x5

torsion is similar to angle-bending motion, provided that the

bond vector is projected perpendicular to rotational axis (see
Fig. 2c). Therefore, the reduced mass for torsion that belongs
to atom j 2 1, j, j 1 1, j 1 2 can be evaluated as that of an
angle

where M is the mass matrix (Mjl 5mj djl with mj being the mass
of atom associated with degree of freedom j), G is the Wilsons
G-matrix,[27] whose inverse provides the effective mass of
internal modes

Itorsion 5

lj21 lj12
lj21 1lj12

(25)

G 21 5B 21 T M B 21

(32)

(33)

As the matrix G21 is not diagonal, the mass associated with

each internal mode cannot be obtained from this matrix.

where
mj21 mj
jjr j21;j jjsinAj 2
mj21 1mj
!
r j21;j  r j;j11
21
Aj 5cos
jjr j21;j jjjjr j;j11 jj

lj21 5

<Ia q_ 2a >
k

Journal of Computational Chemistry 2015, DOI: 10.1002/jcc.23822

(26)

(27)

Computational Details
The vibrational DoS of oxygen, water, hydrogen peroxide,
methanol, hexane, and ubiquitin are evaluated based on velocity in Cartesian and internal coordinate systems. Table 1
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Table 1. Systems studied in this work.

System
Oxygen
Flexible water
Hydrogen
peroxide
Methanol
Hexane
Ubiquitin
(in water)

Num. of
Ensemble molecules

Condition

NVT
NVT
NVT

1000
1000
1000

300 K, 5.5 3 1025 m3/mol

300 K, 2.75 3 1025 m3/mol
300 K, 5.5 3 1025 m3/mol

NVT
NVT
NPT

1000
1000
1 (5738)

300 K/800 K, 5.5 3 1025 m3/mol

300 K/800 K, 1.5 3 1024 m3/mol
310 K, 1 atm

summarizes all the systems and conditions studied in this work.

Oxygen, water, and hydrogen peroxide molecules are used to
represent standard diatomic, triatomic, and tetratomic models.
The details of their force field parameters are provided in Supporting Information. The interactions for methanol and hexane
are described by the OPLS-AA force field,[36,37] and ubiquitin is
described by AMBER03 force field.[38] Open software GROMACS[21] is used for molecular dynamics simulations. For simulations in pure liquid phase, 1000 molecules are randomly inserted
into a 3D periodic box of desired density (0.58 g/cm[3]) using the
Packmol program.[39] Each system was first stabilized with energy
minimization and then simulated under constant temperature
(300 or 800 K) and constant volume for 1 ns with a timestep of 1
fs for equilibration. An additional 200-ps simulation was subsequently performed and the trajectory recorded every 4 fs for the
DoS analysis. Note that the simulation procedure for ubiquitin (1
ubiquitin submerged in 5738 TIP3P water[40]) follows Ref. [41] The
V-rescale algorithm in GROMACS is applied with time constant
0.1 ps to control the temperature. The nonbond and electrostatic
cutoff are both set to 10 A. Particle-Mesh Ewald (PME) is used to
,
calculate long range interactions. The Fourier spacing is 1.2 A
and the PME order is 4. Once the simulation is completed, the
total atomic velocity in each recorded timestep is further decomposed into translational, rotational, and vibrational velocities [eqs.
(5)(8)]. The vibrational velocities are then converted into internal
velocities by Wilsons B-matrix [eq. (11)]. The elements of B-matrix
are calculated from the derivative of internal coordinate displacement with respect to perturbation of Cartesian coordinate by
central difference method. In other words, the change of internal
coordinates (qa ) corresponding to the small displacement of
degree of freedom xb in Cartesian coordinate (both xb1 h and
xb2 h with h 5 1026 A) are used to determine Bab [eq. (10)]. The
reported DoS here are averaged from 10 DoS calculations using
the final 200-ps trajectory (i.e., 20 ps each). The minimum and
maximum frequencies are 0 and 4168.44 cm21, respectively, with
a resolution of 1.112 cm21.

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coordinate systems differ. In Cartesian coordinates, the DoS is

split into two peaks around the actual bond stretching frequency
21
(698
). Note that the theoretical frequency obtained using
p
cm

k=l=2p is 694 cm21. This is the well-known rovibrational coupling in diatomic species.[42] However, only one peak at the same
bond stretching frequency is observed when the internal velocity
is used for the calculation of DoS. In this case, the bond stretching velocity determined from the Wilsons B-matrix is identical to
the velocity projection of atomic vibration along the bond direction. In other words, the velocity component perpendicular to
bond direction (resulting in rotation) is removed. As a result, we
observe a clean peak of bond stretching in the internal DoS of
diatomic species. The internal DoS has the advantage of distinguishing peaks from rotation and internal vibrations.

DoS of water
The next simplest possible case is a triatomic species, such as
water, which contains two bond stretchings and one anglebending modes. Figure 4 illustrates that the DoS from the two
coordinate systems are similar with the bending mode located
at 1440 cm21 and symmetric stretching at 3675 cm21, and
asymmetric stretching at 3700 cm21. However, it is possible to
decompose the internal DoS to contributions from each individual degree of freedom: one bond bending and two equivalent bond stretchings. In such a case, each internal bond

Results and Discussion

DoS of oxygen
Oxygen is used as the simplest type of systems with one internal
motion, bond stretching. Figure 3 compares the DoS of oxygen
evaluated using Cartesian and internal velocities. It can be seen
that even for the simplest case DoS determined from different

Figure 3. DoS (bottom) and its integration (top) of oxygen at 300 K and
5.5 31025 m3/mol. (Blue: bond; green: Cartesian).

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seen that the system exhibit one degree of freedom at

700 cm21, another one at 950 cm21, two more at 1320 cm21,
and remaining two at 3790 cm21. Although the overall DoS
from the two coordinate systems are similar, the internal DoS
allows for the identification of normal modes with internal
molecular degree of freedom. For example, the lowest frequency mode at 700 cm21 comes from the torsional degrees of
freedom (orange curve). The second peak at 950 cm21 in Cartesian DoS involves OO bond stretching, in additional to a small
portion of angle bending. The third peak at 1320 cm21 corresponds mostly two HOO angle bending and some OO bond
stretching (see inset plot), and the highest frequency peak
at 3790 cm21 comes from OH stretching. Note that the
summation of degree of freedom integration for internal
DoS up to highest frequency should be equal to that from Cartesian DoS.
DoS of methanol
The simulation of methanol molecule is used to examine the
free rotor behavior of dihedral torsion (HACAOAH). Methanol
contains six atoms, five bonds (three CH, one CO, and one OH),

Figure 4. DoS (bottom) and its integration (top) of flexible water

at 300 K and 2.75 3 1025 m3/mol. (Blue: bond; red: angle; green:
Cartesian).

stretching contains both symmetric and asymmetric modes. It is

noted that a small bending peak exist in the bond-stretching
frequency (around 3650 cm21). This implies that the normal
mode of bond stretching involved symmetric bond stretching
and a small portion of internal angle motion. Similarly, one
observes the internal bond stretching (blue curve) having a
very small peak at 1450 cm21, implying that the bond stretchings (normal mode) are accompanied with angle bending.
These results are consistent with the fact that the internal
modes are not orthogonal, and the normal modes are combinations of the internal modes. The comparison of Cartesian DoS
and internal DoS thus allows for identification of all the internal
modes associated with a certain normal mode.
DoS of hydrogen peroxide
Hydrogen peroxide is used as an example of the simplest molecule that has internal rotation. The torsional mode is relatively
soft compared to angle and bond motions and is responsible
for conformation changes of large species. There are six internal
modes in H2O2, one dihedral torsion (HOOC), two angle bendings (HOO), and three bond stretchings (two HO, one OO). With
the aid of the integration of DoS (top figure of Fig. 5), it can be
6

Journal of Computational Chemistry 2015, DOI: 10.1002/jcc.23822

Figure 5. DoS (bottom) and its integration (top) of hydrogen peroxide

at 300 K and 5.5 3 1025 m3/mol. (Blue: bond; red: angle; orange: dihedral; green: Cartesian; purple: OO bond; pink: OH bond).

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Figure 6. DoS (bottom) and its integration (top) of methanol at a) 300 K and b) 800 K and 5.5 3 1025 m3/mol, respectively. (Blue: bond; red: angle; orange:
dihedral; green: Cartesian). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 7. DoS (bottom) and its integration (top) of hexane at a) 300 K and b) 800 K and 1.5 3 1024 m3/mol, respectively. (Blue: bond; red: angle; orange:
dihedral; green: Cartesian). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

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significant steric hindrance of hexane. Another significant difference between methanol and hexane cases is observed from
Cartesian DoS at low frequency. For methanol, the Cartesian
DoS is smaller than that from internal DoS at low frequency,
while for hexane, the opposite behavior is shown (green curve

Figure 8. DoS (bottom) and its integration (top) of united-atom hexane

with fixed bond at 300 K. (Red: angle; orange: dihedral; green: Cartesian;
purple: angle1dihedral). [Color figure can be viewed in the online issue,
which is available at wileyonlinelibrary.com.]

seven angles (three HCH, three HCO, and one COH), and three
dihedrals (three HCOH). Figures 6a and 6b illustrate the DoS
methanol at 300 and 800 K, respectively. It can be seen that the
normal modes (green curve) below 800 cm21 constitute solely
from the dihedral torsion (orange curve). At low temperature
(300 K), the dihedral torsion is under hindered rotation (peaks
at 100 and 650 cm21) with a small fraction of diffusional rotation (indicated by a finite intensity at zero frequency). As the
temperature increases to 800 K, the low frequency peak disappears and the internal rotation diffusion is enhanced significantly. At high temperature (800 K), the dihedral torsion
(HACAOAH) may overcome the torsional barrier and become a
free internal rotor. Although the red shift of the hindered dihedral rotation is captured by the Cartesian DoS, the enhancement of rotational diffusion cannot be observed. This shows the
advantage of the internal DoS for analyzing the transition of
internal rotations of conformationally flexible molecules.
DoS of hexane
Hexane is chosen as a representative for species containing
multiple dihedral torsions. Figure 7 presents DoS of liquid hexane at 300 and 800 K, respectively. The torsion DoS shows less
diffusive motion compared to that of methanol due to a more
8

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Figure 9. The torsional DoS of the first to fifth dihedral angles (ae, respectively) for hexane at 300(blue) and 800 K (red). [Color figure can be viewed
in the online issue, which is available at wileyonlinelibrary.com.]

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dom). It can be seen that the integration of the Cartesian DoS

(green curve) is almost always higher than that of the internal
DoS (purple curve) before 400 cm21. The differences between
the two are compensated by the angle bending at 410 cm21,
where the Cartesian DoS shown one degree of freedom and
the internal DoS shows two degrees of freedom. Therefore, the
enhanced low frequency normal modes (e.g., <200 cm21) are
the result of coupling between the internal dihedral torsion and
angle bending. One possible explanation is that the coupling of
these nonorthogonal motions results in anharmonic vibrations
that appears at low frequencies in the normal modes.
The internal DoS method allows us to study specific mode
with ease. Figure 9 illustrates the five internal DoS dihedral torsions (for all-atom hexane) on the main chain at 300 and 800 K,
respectively. The terminals are HCCC dihedral torsions, and the
rest are CCCC dihedral torsions. Because of symmetry, the first
and the fifth dihedrals (Figs. 9a and 9e) and the second and the
fourth dihedrals (Figs. 9b and 9d) exhibit similar internal DoS,
respectively. The DoS of middle three torsions (Figs. 9b9d) are
similar and significantly different from the two end dihedrals. At
300 K, the terminal torsions are mostly hindered rotation (peak
appears at higher frequency), and at 800 K, the motion shows
enhanced free rotation. The enhancement of free dihedral rotation with temperature is less significant for the middle dihedrals. Therefore, the internal DoS allows for a clear distinction of
different dynamic behaviors of internal rotations that are
responsible for the change of molecular conformation.
DoS of ubiquitin
Figure 10. DoS (bottom) and its integration (top) of ubiquitin at 310 K.
(Red: angle; orange: dihedral; green: Cartesian). [Color figure can be viewed
in the online issue, which is available at wileyonlinelibrary.com.]

above the orange curve). The significantly enhanced low frequency normal modes is examined using united-atom hexane
(DREIDING force field[43]) with all bonds fixed. In this case,
there are seven internal degrees of freedom: four CCC angles
and three dihedral torsions.
Figure 8 shows the DoS for the united hexane from the Cartesian and internal velocities. From the internal DoS, the three
dihedral torsion concentrated around 140 cm21, and the four
angle bending appear at 300 (one degree of freedom), 340
(one degree of freedom), and 410 cm21 (two degrees of free-

The proposed method can be easily applied to macromolecules.

To illustrate this, the DoS of an ubiquitin molecule submerged
in water at 310K is shown in Figure 10. All the bonds are fixed.
There are 2257 angles and 4207 dihedrals for ubiquitin, and the
internal DoS is the summation of individual DoS for angles and
dihedrals, respectively. In principle, the evaluation of B-matrix
scales as Nk[2]. However, one can update those internal DOFs
that constitute the atom being perturbed, and the evaluation
time can reduce to scale as Nk. (For example, if we perturb the
hydrogen on oxygen of methanol, we only need to calculate
the differentiation of OH bond only and not other internal
bonds). For ubiquitin, the calculation speed becomes 26 times
faster, if the above procedure is applied. The Cartesian DoS has
significantly higher intensity at low frequency, while internal
DoS shows more reasonable distribution for both angles and

Table 2. Vibrational temperature (K) and mass factor c determined from Cartesian (Vib) and from internal coordinates (Bond; Angle; Dihedral) using
reduced mass.

Oxygen
Water
Hydrogen peroxide
Methanol
Methanol
Hexane
Hexane
Ubiquitin

Tvib

TB

cB

300
300
300
300
800
300
800
310

302.6 6 1.6
302.8 6 3.2
302.6 6 1.1
302.0 6 1.1
804.1 6 1.6
300.4 6 0.4
800.8 6 0.5
310.0 6 0.0

302.6 6 1.6
304.2 6 4.9
306.9 6 1.3
308.7 6 1.8
818.3 6 3.0
304.0 6 1.1
810.9 6 1.1

1.000
0.995
0.986
0.978
0.982
0.988
0.988

TA

cA

TD

cD

302.3 6 1.3
300.7 6 1.6
306.4 6 2.3
818.4 6 2.4
314.0 6 1.0
836.3 6 1.0
263.0 6 0.94

1.001
1.006
0.985
0.982
0.957
0.957
1.179

302.4 6 2.0
308.6 6 0.9
825.7 6 3.2
321.9 6 0.8
866.9 6 1.0
349.2 6 1.7

1.000
0.978
0.974
0.933
0.923
0.888

Journal of Computational Chemistry 2015, DOI: 10.1002/jcc.23822

FULL PAPER

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Figure 11. Dihedral velocity (recorded every 4 fs) obtained from Wilsons B-matrix (blue) and from time differentiation (red) for a) a single methanol and b)
a single hexane at 800 K. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

dihedrals. This is similar to the previous hexane case. Although

it is straightforward to analyze a subset of internal motions (as
in previous section for hexane) or examine the change of internal dynamics due to temperature, pressure, or chemical modifications, they are beyond the scope of this work. The results
here show that the internal DoS can be obtained with ease for
flexible molecules with holonomic constraints.
Reduced mass effect on temperature
Table 2 lists the vibrational temperature from Cartesian and
from internal coordinates for all systems in this study. The
deviation of the internal mode temperature from the vibrational temperature is an indication of either a poor thermal
equilibration or of an error caused by the calculation of
reduced mass. Such deviation is quantified by the mass factor ca [eq. (31)], the ratio of vibrational temperature to the
internal mode temperature. For oxygen, the temperature
determined from reduced mass is exactly the same as that
from Cartesian, that is, c 5 1. For water, the bond and
angle temperatures are still close (within statistical error) to
Cartesian vibrational temperature. The deviation increases
slightly with the size of the molecules: <2% for hydrogen
peroxide, <3% for methanol, <2% for the bonds of hexane,
<5% for the angles of hexane, and <8% for the dihedrals
of hexane. For ubiquitin, the deviation increases to about
15%. It should be noted that the DoS itself is not affected
by reduced mass as long as a consistent temperature is
used in eq. (18). Nevertheless, the reduced mass is essential
for temperature calculation and other analysis such as thermodynamic property calculations.[58] The mass factor can
be used to correct for any error introduced in the reduced
mass calculation and obtain an effective mass for internal
modes based on the equipartition theorem.
Comparison of Wilsons method with numerical method
Here we compare the velocity in internal coordinates obtained
from the Wilsons B-matrix [eq. (11)] and direct numerical
derivatives [eqs. (15)(17)]. The Wilson B-matrix usually applies
10

Journal of Computational Chemistry 2015, DOI: 10.1002/jcc.23822

to semirigid molecule with small displacements. It is important

to examine if this approach works for slow vibrations and rotational diffusion. Figure 11 compares the dihedral velocity converted from Cartesian vibrational velocity with that from
numerical differentiation for methanol (Fig. 11a) and hexane
(Fig. 11b) at 800 K. It can be seen the dihedral velocity from
both methods are nearly identical. The agreement remains the
same for hexane which contains multiple dihedral torsions
(the terminal torsion is shown for comparison). These results
suggest that Wilsons B-matrix is of general validity and can be
applied to complex macromolecular systems.

Conclusions
In this work, we present the first thorough discussion on internal coordinate DoS calculation from molecular dynamics simulation. The internal DoS studied cover from the simplest
diatomic molecule to structurally complicated ubiquitin. The
internal DoS would be identical to that of Cartesian DoS in the
limit of purely harmonic system (e.g., low temperature crystal).
In general, several differences exist in the two representations
of DoS. First, the rovibrational coupling in Cartesian DoS is not
present in internal DoS. Second, the transition of dihedral
motion from hindered rotation, to hindered diffusive, to free
rotation can be easily identified in internal DoS but less
obvious in Cartesian representation. Finally, the enhanced low
frequency modes due to coupling of internal motions in Cartesian DoS does not appear in internal DoS.
There are several advantages to obtaining internal DoS in
additional to the common Cartesian DoS. First of all, the internal motion associated with any specific normal mode found in
Cartesian DoS can be easily identified. Furthermore, the internal rotation, which is responsible for conformation change of
macromolecules, can be quantified with internal DoS. More
importantly, each of the internal modes of a system can be
separated from the total and examined. This allows for a
detailed analysis of the dynamics of the system. The method
present here is general and is applicable to any molecular systems, small or large, fully flexible or with constraints. It is
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believe that the method would be useful to analyzing complex

systems including biomolecules and polymers.

Acknowledgments
The computation resources from the National Center for HighPerformance Computing of Taiwan and the Computing and Information Networking Center of the National Taiwan University are
acknowledged.

Appendix

The procedure of calculating B matrix is outlined below.

1. Take connectivity of bond, angle, and dihedral from MD
topology file. Note that the total number of internal
modes can be greater than the internal degrees of freedom (3N 2 6). For example, hexane molecule (N 5 20) has
19 bonds, 27 angles, and 45 dihedral torsions. The total
number of internal modes are 91. The total internal
degrees of freedom is 54: 19 (20 2 1) for bond, 18
(20 2 2) for angle, and 17 (20 2 3) for dihedral torsions.
) is introduced to each
2. A small displacement (h 5106 A
degrees of freedom (b) in the Cartesian coordinates (x, y,
or z) both in the forward and backward directions, that
is, xb 1 h and xb 2 h.
3. For each perturbation (xb 1 h or xb 2 h), the resulting Cartesian coordinates are converted to internal coordinates [eqs.
(12)(14)], then numerical differentiation is calculated to
obtain for every internal coordinate. Repeat steps (2) and (3)
for every degree of freedom in the Cartesian coordinates.

Note that the method proposed here does not require the
inverse of B as in the Wilsons method [eq. (33)], and
thus B does not have to be a square matrix. It is thus convenient to separate the total B into components of bonds
(B ), angles (B
), and dihedral torsions (B
). For
bond

angle

dihedral

[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]

[25]
[26]

[27]
[28]
[29]
[30]
[31]
[32]
[33]

hexane, the dimension for each matrix is 19 3 60, 27 3

60 and 45 3 60, respectively. Therefore, we have determined the internal DoS different components separately
and renormalize to obtain the total DoS as in eq. (18).

[34]

Keywords: density of state  velocity spectrum  Cartesian

coordinates  internal coordinates  normal modes  molecular
dynamics simulation

[37]
[38]
[39]

[35]
[36]

[40]

How to cite this article: P.-K. Lai, S.-T. Lin. J. Comput. Chem.
2015, DOI: 10.1002/jcc.23822

Additional Supporting Information may be found in the

online version of this article.

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[2] D. Beeman, R. Alben, Adv. Phys. 1977, 26, 339.

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Received: 12 October 2014

Revised: 30 November 2014
Accepted: 2 December 2014
Published online on 00 Month 2014

Journal of Computational Chemistry 2015, DOI: 10.1002/jcc.23822

11