sampling realistic protein conformations using local structural bias抽样实际蛋白质构象使用本地结构性偏见.pdfVIP

Sampling Realistic Protein Conformations Using Local Structural Bias 1* 2 1 Thomas Hamelryck , John T. Kent , Anders Krogh 1 Bioinformatics Center, Institute of Molecular Biology and Physiology, University of Copenhagen, Copenhagen, Denmark, 2 The Department of Statistics, The University of Leeds, Leeds, West Yorkshire, United Kingdom 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. Citation: Hamelryck T, Kent JT, Krogh A (2006) Sampling realistic protein conformations using local structural bias. PLoS Comput Biol 2(9): e131. DOI: 10.1371/journal.pcbi. 0020131 Introduction weights. The subject of this paper is the generation of decoys,