title: Sampling realistic protein conformations using local structural bias.
abstract: The prediction of protein structure from sequence remains a major unsolved problem in biology. The most successful protein structure prediction methods make use of a divide-and-conquer strategy to attack the problem: a conformational sampling method generates plausible candidate structures, which are subsequently accepted or rejected using an energy function. Conceptually, this often corresponds to separating local structural bias from the long-range interactions that stabilize the compact, native state. However, sampling protein conformations that are compatible with the local structural bias encoded in a given protein sequence is a long-standing open problem, especially in continuous space. We describe an elegant and mathematically rigorous method to do this, and show that it readily generates native-like protein conformations simply by enforcing compactness. Our results have far-reaching implications for protein structure prediction, determination, simulation, and design.
authors.affiliation: Bioinformatics Center, Institute of Molecular Biology and Physiology, University of Copenhagen, Copenhagen, Denmark. thamelry@binf.ku.dk
authors.forename: Thomas
authors.initials: T
authors.lastname: Hamelryck
authors.forename: John T
authors.initials: JT
authors.lastname: Kent
authors.forename: Anders
authors.initials: A
authors.lastname: Krogh
mesh_terms: D000595:Amino Acid Sequence; D019295:Computational Biology; D003198:Computer Simulation; D008958:Models, Molecular; D011336:Probability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins