Protein Folding

Proteins are linear chains of amino acids that adopt unique three-dimensional structures which allow them to carry out intricate biological functions. All of the information needed to specify a protein's three-dimensional structure is contained within its amino-acid sequence, the primary structure. Given suitable conditions, most small proteins will spontaneously fold to their native states [9]. In protein folding, one wants to predict the tertiary or globally folded three-dimensional structure from the primary structure or from the secondary structure (information about local folding). Although much is known of the structural details of the native, folded conformation of proteins, very little is known about the actual folding process. Protein folding or protein structure prediction remains one of the most important unsolved problems in molecular biology. The goal of predicting the structure of a protein sequence is to understand its function [11,92,108,150]. Knowing the structure also enables us to perform rational drug design [22], understand substrate and ligand binding, and design novel proteins [33].

To observe global folding effects, simulations of milli-second time scales to a second are essential. The project concerns the enlargement of the scope of the existing methods of molecular dynamics to the study of structure and dynamics of larger biological macromolecules by introducing new, explicit, symplectic integration algorithms for Hamiltonian systems and their parallel implementation on distributed memory computers and on emerging clusters of shared memory computers. This will provide savings on experimental work by realistic prediction of structure (conformation, interactions, thermodynamics). Processes of interest include the folding of small proteins, and side-chain protein dynamics.