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
– 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
– 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.
– 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