Computer simulation of proteins : methodology and applications

Abstract

During the last decade it has become feasible to simulate the behaviour of biologically relevant molecules on a computer. The method of molecular dynamics (MD) solves Newton’s equations of motion for a molecular system, which results in trajectories for all atoms in the system. From these atomic trajectories a variety of properties can be calculated.Computer simulation of molecular systems aims at macroscopic behaviour to be computed from microscopic interactions. The main contributions of the microscopic point of view are(1)understanding of the relation between atomic properties and molecular behaviour,(2) interpretation of experimental results, (3)prediction of molecular behaviour and (4)the capability to simulate under conditions that are hard to reach in the laboratory.One of the two basic problems in the field of molecular modelling and simulation is the derivation of a sufficiently accurate interaction energy function or force field for the molecular system of interest. The other basic problem is how to efficiently search the vast conformational space which is spanned by all possible molecular conformations for the global low (free) energy regions which will be populated by a molecular system in thermal equilibrium.With respect to the second basic problem various time-saving techniques which have and have not yet been tested in practical simulations will be reviewed. Besides, some practical applications of computer simulation in the field of (bio)chemistry will be discussed.