title: Reconstruction and stability of secondary structure elements in the context of protein structure prediction.
abstract: Efficient and accurate reconstruction of secondary structure elements in the context of protein structure prediction is the major focus of this work. We present a novel approach capable of reconstructing alpha-helices and beta-sheets in atomic detail. The method is based on Metropolis Monte Carlo simulations in a force field of empirical potentials that are designed to stabilize secondary structure elements in room-temperature simulations. Particular attention is paid to lateral side-chain interactions in beta-sheets and between the turns of alpha-helices, as well as backbone hydrogen bonding. The force constants are optimized using contrastive divergence, a novel machine learning technique, from a data set of known structures. Using this approach, we demonstrate the applicability of the framework to the problem of reconstructing the overall protein fold for a number of commonly studied small proteins, based on only predicted secondary structure and contact map. For protein G and chymotrypsin inhibitor 2, we are able to reconstruct the secondary structure elements in atomic detail and the overall protein folds with a root mean-square deviation of <10 A. For cold-shock protein and the SH3 domain, we accurately reproduce the secondary structure elements and the topology of the 5-stranded beta-sheets, but not the barrel structure. The importance of high-quality secondary structure and contact map prediction is discussed.
authors.affiliation: Keck Graduate Institute of Applied Life Sciences, Claremont, California, USA.
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Podtelezhnikov
authors.forename: David L
authors.initials: DL
authors.lastname: Wild
mesh_terms: D000465:Algorithms; D001185:Artificial Intelligence; D001426:Bacterial Proteins / Q000737:chemistry; D003198:Computer Simulation; D004926:Escherichia coli; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008958:Models, Molecular; D009010:Monte Carlo Method; D009419:Nerve Tissue Proteins / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D010940:Plant Proteins / Q000737:chemistry; D055550:Protein Stability; D017433:Protein Structure, Secondary; D013696:Temperature; D018909:src Homology Domains; D019061:src-Family Kinases / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; C029152:G-substrate; D009419:Nerve Tissue Proteins; D010455:Peptides; D010940:Plant Proteins; C093336:chymotrypsin inhibitor 2; C077188:cold-shock protein CspB, Bacteria; D019061:src-Family Kinases