FAMSD: A Powerful Protein Modeling Platform that CombinesAlignment Methods, Homology Modeling, 3D Structure QualityEstimation and Molecular Dynamics

摘要

The prediction of a protein three-dimensional (3D) structure is one of the most important challenges in com-putational structural biology. We have developed an automatic protein 3D structure prediction method calledFAMSD. FAMSD is based on a comparative modeling method which consists of the following four steps: (1) gen-erating and selecting sequence alignments between target and template proteins; (2) constructing 3D structuremodels based on each selected alignment; (3) selecting the best 3D structure model and (4) refining the selectedmodel. In the FAMSD method, sequence alignment programs such as a series of BLAST programs, SP3 andSPARKS2 programs, the homology modeling program FAMS (Full Automatic Modeling System), the modelquality estimation program CIRCLE and the molecular dynamics program APRICOT were used in combinationto construct high quality protein models. To assess the FAMSD method we have participated in the 8th CriticalAssessment of Techniques for Protein Structure Prediction (CASP8) experiment. The results of our original as-sessment indicate that the FAMSD method offers excellent capability in packing side-chains with the correct tor-sion angles while avoiding the formation of atom—atom collisions. Since side-chain packing plays a significantrole in defining the biological function of proteins, this method is a valuable resource in biological, pharmaceuti-cal and medicinal research efforts.