Abstract: The invention provides a new, efficient method for the assembly of protein tertiary structure from known, loosely encoded secondary structure constraints and sparse information about exact side chain contacts. The method is based on a new method for the reduced modeling of protein structure and dynamics, where the protein is described by representing side chain centers of mass rather than alpha-carbons. The model has implicit, built-in multi-body correlations that simulate short- and long-range packing preferences, hydrogen bonding cooperativity, and a mean force potential describing hydrophobic interactions. Due to the simplicity of the protein representation and definition of the model force field, the Monte Carlo algorithm is at least an order of magnitude faster than previously published Monte Carlo algorithms for three-dimensional structure assembly.

Abstract: A computer system and method are disclosed for determining a protein's tertiary structure from a primary sequence of amino acid residues. The system uses a dynamic Monte Carlo method with Metropolis sampling criterion, and a selected (2,1,0) lattice model, to simulate protein folding during the transition of the protein from an unfolded (denatured) state to its native, folded state. The system generates, for display, a folding trajectory representing successive three-dimensional images of the protein at a level of two Angstrom resolution as it folds to its native conformation. The system permits interaction between all proximate pairs of sidechains of the protein and provides faster processing through the use of the lattice.