title: Fast and accurate side-chain topology and energy refinement (FASTER) as a new method for protein structure optimization.
abstract: We have developed an original method for global optimization of protein side-chain conformations, called the Fast and Accurate Side-Chain Topology and Energy Refinement (FASTER) method. The method operates by systematically overcoming local minima of increasing order. Comparison of the FASTER results with those of the dead-end elimination (DEE) algorithm showed that both methods produce nearly identical results, but the FASTER algorithm is 100-1000 times faster than the DEE method and scales in a stable and favorable way as a function of protein size. We also show that low-order local minima may be almost as accurate as the global minimum when evaluated against experimentally determined structures. In addition, the new algorithm provides significant information about the conformational flexibility of individual side-chains. We observed that strictly rigid side-chains are concentrated mainly in the core of the protein, whereas highly flexible side-chains are found almost exclusively among solvent-oriented residues.
authors.affiliation: AlgoNomics NV, Gent-Zwijnaarde, Belgium. Johan.Desmet@algonomics.com
authors.forename: Johan
authors.initials: J
authors.lastname: Desmet
authors.forename: Jan
authors.initials: J
authors.lastname: Spriet
authors.forename: Ignace
authors.initials: I
authors.lastname: Lasters
mesh_terms: D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D000596:Amino Acids; D011506:Proteins