Brief History of Computer Simulations

•1953:Equation of state calculations by fast computing mechines (1953)

N Metropolis,A W Rosenbluth, M N Rosebluth, A H Teller

This paper applied Monte-Carlo technique to solving physical equations of a system composed of interacting individual molecules. First step is to generate a subset of random number to represent conformational space, then using exponent of the energy as probability filter.

• 1956: Phase Transition for a Hard Sphere System

B. J. Alder and T. E. Wainwright

– First “proper” molecular dynamics (MD) simulation: dynamics of an

assembly of hard spheres

• (1958: A three-dimensional model of the myoglobin molecule obtained by x-ray analysis)

First X-ray structure of protein

• 1964: Correlations in the Motion of Atoms in Liquid Argon

A. Rahman

– MD simulation of liquid Ar. He is known as the father of molecular dynamics

• 1969: Barker and Watts

– Monte Carlo simulation of water

• 1971: Rahman and Stillinger

– MD simulation of water

• Water simulations are a greater challenge than liquid Ar since,

in addition to van der Waal’s interactions, there are Coulomb

and hydrogen bond interactions.

1970s: Simulations of small solutes and peptides

•1975 Computer simulation of protein folding

Michael Levitt Arich Warshel

First published MD simulation of protein, and sucessfully refold BPTI from an open-chain conformation(terminal helix) by simplifiled representation of protein structure.

• 1977: McCammon, Gelin, Karplus

– First MD simulation of proteins

1980s:

– Simulations of biomolecules

– Free energy calculations

– Protein-ligand docking calculations

• 1979:Dynamics of ligand binding to heme protein

D A Case, M Karplus

-This is the first simulation of ligand moving through the protein.

• 1988:Accurate simulation of protein dynamics in solution

Michael Levitt and R Sharon

- First simulation of a protein in explicit waters.

• 1990s:

– Continued development of potentials and sampling techniques

• 1998: Duan and Kollman: 1µs MD simulation of the folding of

the Villin headpiece in explicit solvent

• 1999: Sugita and Okamoto: replica exchange molecular

dynamics