METHOD OF DETERMINING THREE-DIMENSIONAL PROTEIN STRUCTURE FROM PRIMARY PROTEIN SEQUENCE

摘要

The Generic Protein method is a computer-implemented system for determining the three-dimensional structure of a protein from its amino acid sequence. The method incorporates a hierarchical approach wherein the number of candidate structures decreases at each step. The starting point is the use of a sequence independent ensemble of compact structures which represents an exhaustive enumeration of all possible self-avoiding folded topologies for a n residue polypeptide. Because the number of candidate conformations is dramatically reduced, recognition filters such as radius of gyration, distribution of hydrophobic residues, and the satisfaction of disulfide constraints can be used to further reduce the number of candidate conformations. The complexity of the initial ab initio structure prediction problem can be reduced to a complexity on the order of a homology modeling exercise. The final refinement step may involve molecular mechanics procedures with explicit solvation parameters on full-atom representations of the remaining candidate structures.