bclfold - de novo prediction of complex and large protein topologies by assembly of secondary structure elementsbclfoldu2014u2014新创的复杂和庞大的蛋白质拓扑预测二级结构元素的组装.pdfVIP

BCL::Fold - De Novo Prediction of Complex and Large Protein Topologies by Assembly of Secondary Structure Elements Mert Karakas¸, Nils Woetzel, Rene Staritzbichler, Nathan Alexander, Brian E. Weiner, Jens Meiler* Department of Chemistry, Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, United States of America Abstract Computational de novo protein structure prediction is limited to small proteins of simple topology. The present work explores an approach to extend beyond the current limitations through assembling protein topologies from idealized a- helices and b-strands. The algorithm performs a Monte Carlo Metropolis simulated annealing folding simulation. It optimizes a knowledge-based potential that analyzes radius of gyration, b-strand pairing, secondary structure element (SSE) packing, amino acid pair distance, amino acid environment, contact order, secondary structure prediction agreement and loop closure. Discontinuation of the protein chain favors sampling of non-local contacts and thereby creation of complex protein topologies. The folding simulation is accelerated through exclusion of flexible loop regions further reducing the size of the conformational search space. The algorithm is benchmarked on 66 proteins with lengths between 83 and 293 amino ˚ acids. For 61 out of these proteins, the best SSE-only models obtained have an RMSD100 below 8.0 A and recover more than 20% of the native contacts. The algorithm assembles protein topologies with up to 215 residues and a relative contact order of 0.46. The method is tailored to be used in conjunction with low-resolution or sparse experimental data sets which often provide restraints for regions of defined se