Molecular Dynamics simulations

Bert de Groot
Max Planck institute for biophysical chemistry
Gttingen, Germany

Molecular Dynamics Simulations

Schrdinger equation

Born-Oppenheimer approximation

Nucleic motion described classically

Empirical force field

Molecular Dynamics Simulations

Interatomic interactions

Molecular dynamics-(MD) simulations of Biopolymers

d2
Motions of nuclei are described classically,
( ) ma 2 R Eel ( R1 ,..., RN ), 1,..., N .
dt
Potential function Eel describes the electronic influence on motions of the nuclei and is
approximated empirically classical MD:

E el

E ibond

Bindungen
i

Bindungs
winkel j

angle
j

Dihedral
winkel k

Covalent bonds
Eibond

exact
=
R=
0

.
rep .
vdW
( ECoul
, E , E , ) ...,

Non-bonded interactions

approximated

K BT {

dihe
k

|R|

ForceField

Molecular Dynamics Simulation

Molecule: (classical) N-particle system
Newtonian equations of motion:

with

d2
mi 2 ri Fi ( r )
dt

Fi (r ) iV (r )

r ( r1 ,..., rN )

Integrate numerically via the leapfrog scheme:

with
t 1fs!

(equivalent to the Verlet algorithm)

BPTI: Molecular Dynamics (300K)

Computational task:
Solve the Newtonian equations of motion:

Non-bonded interactions

Lennard-Jones potential

Coulomb potential

Use of constraints to
increase the integration step

The SHAKE algorithm

t = 1fs --> 2 fs

Molecular dynamics is very expensive ...

Example: F1-ATPase in water (183 674 atoms), 1 nanosecond:
106 integration steps
8.4 * 1011 flop per step [n(n-1)/2 interactions]

total:

8.4 * 1017 flop

on a 100 Mflop/s workstation:

ca 250 years

...but performance has been improved by use of:

multiple time stepping

ca. 25 years

+ structure adapted multipole methods

ca.

6 years

+ FAMUSAMM

ca.

2 years

+ parallel computers

ca. 55 days

Limits of MD-Simulations
classical description:
chemical reactions not described
poor description of H-atoms (proton-transfer)
poor description of low-T (quantum) effects
simplified electrostatic model
simplified force field
only small systems accessible (104 ... 106 atoms)
only short time spans accessible (ps ... s)

MD-Experiments with Argon Gas

Role of environment - solvent

explicit
or
implicit?

box
or
droplet?

Surface (tension) effects?

periodic boundary conditions
and the minimum image convention

Proteins jump between many, hierarchically ordered

conformational substates

H. Frauenfelder et al., Science 229 (1985) 337

Reversible Folding Dynamics of a -Peptide

X. Daura, B. Jaun, D. Seebach, W.F. van Gunsteren, A.E. Mark, J. Mol. Biol. 280 (1998) 925

MD Simulations
external coupling:
temperature (potential truncation, integration errors)
pressure (density equilibration)
system translation/rotation
analysis
energies (individual terms, pressure, temperature)
coordinates (numerical analysis, visual inspection!)
mechanisms