title: Protein structure determination by conformational space annealing using NMR geometric restraints.
abstract: We have carried out numerical experiments to investigate the applicability of the global optimization method of conformational space annealing (CSA) to the enhanced NMR protein structure determination over existing PDB structures. The NMR protein structure determination is driven by the optimization of collective multiple restraints arising from experimental data and the basic stereochemical properties of a protein-like molecule. By rigorous and straightforward application of CSA to the identical NMR experimental data used to generate existing PDB structures, we redetermined 56 recent PDB protein structures starting from fully randomized structures. The quality of CSA-generated structures and existing PDB structures were assessed by multiobjective functions in terms of their consistencies with experimental data and the requirements of protein-like stereochemistry. In 54 out of 56 cases, CSA-generated structures were better than existing PDB structures in the Pareto-dominant manner, while in the remaining two cases, it was a tie with mixed results. As a whole, all structural features tested improved in a statistically meaningful manner. The most improved feature was the Ramachandran favored portion of backbone torsion angles with about 8.6% improvement from 88.9% to 97.5% (P-value <10(-17)). We show that by straightforward application of CSA to the efficient global optimization of an energy function, NMR structures will be of better quality than existing PDB structures.
authors.affiliation: Center for in Silico Protein Science, Korea Institute for Advanced Study, Seoul, 130-722, Korea.|Center for Advanced Computation, Korea Institute for Advanced Study, Seoul, 130-722, Korea.
authors.forename: Keehyoung
authors.initials: K
authors.lastname: Joo
authors.affiliation: Center for in Silico Protein Science, Korea Institute for Advanced Study, Seoul, 130-722, Korea.|School of Computational Sciences, Korea Institute for Advanced Study, Seoul, 130-722, Korea.
authors.forename: InSuk
authors.initials: I
authors.lastname: Joung
authors.affiliation: Korean Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Korea.|Department of Nanobiotechnology and Bioinformatics, University of Sciences and Technology, Daejeon, 305-350, Korea.
authors.forename: Jinhyuk
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Mathematics, Kwangwoon University, Nowon-Gu, Seoul, 139-701, Korea.
authors.forename: Jinwoo
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Yonsei University, Seodaemun-Gu, Seoul, 120-749, Korea.
authors.forename: Weontae
authors.initials: W
authors.lastname: Lee
authors.affiliation: Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, 20852.
authors.forename: Bernard
authors.initials: B
authors.lastname: Brooks
authors.affiliation: Center for in Silico Protein Science, Korea Institute for Advanced Study, Seoul, 130-722, Korea.|Department of Physics, University of Suwon, Hwaseong-Si, Gyeonggi-Do, 445-743, Korea.
authors.forename: Sung Jong
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Center for in Silico Protein Science, Korea Institute for Advanced Study, Seoul, 130-722, Korea.|School of Computational Sciences, Korea Institute for Advanced Study, Seoul, 130-722, Korea.
authors.forename: Jooyoung
authors.initials: J
authors.lastname: Lee
mesh_terms: D030562:Databases, Protein; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins
keywords: NMR restraint; ambiguous distance correction; global optimization; protein structure determination