Prediction of protein side-chain conformations from local three-dimensional homology relationships.
A method for predicting the conformations of protein side-chains, starting from main-chain co-ordinates alone, is described. The method involves the comparison of the local environment of each residue whose side-chain conformation is to be predicted with a database of local environments for the same residue type constructed from an analysis of high-resolution protein structures. Local environments are described in terms of the residue type and location in space of residues that interact with the side-chain of interest. The best (most three-dimensionally homologous) few matches to each residue are then input to a Monte-Carlo procedure to give a final predicted structure. The method has been tested on a selection of eight proteins, ranging in size from 46 to 323 amino acid residues. The average side-chain atom root-mean-square deviation between the actual and predicted structures is 1.71 A taken over all residues, and 1.00 A if restricted to buried residues. Over all residues, an average of 59.8% of all side-chain dihedral angles are predicted within +/- 30 degrees of the crystal structure values. Considering buried residues only, this rises to 79.6%.
Laughton
C A
CA
CRC Biomolecular Structure Unit, Institute of Cancer Research, Sutton, Surrey, U.K.
D007611:Aprotinin / Q000737:chemistry / Q000648:ultrastructure; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D005418:Flavodoxin / Q000737:chemistry / Q000648:ultrastructure; D008958:Models, Molecular; D008962:Models, Theoretical; D009010:Monte Carlo Method; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D005418:Flavodoxin; D007611:Aprotinin