title: A Stochastic Point Cloud Sampling Method for Multi-Template Protein Comparative Modeling.
abstract: Generating tertiary structural models for a target protein from the known structure of its homologous template proteins and their pairwise sequence alignment is a key step in protein comparative modeling. Here, we developed a new stochastic point cloud sampling method, called MTMG, for multi-template protein model generation. The method first superposes the backbones of template structures, and the Cα atoms of the superposed templates form a point cloud for each position of a target protein, which are represented by a three-dimensional multivariate normal distribution. MTMG stochastically resamples the positions for Cα atoms of the residues whose positions are uncertain from the distribution, and accepts or rejects new position according to a simulated annealing protocol, which effectively removes atomic clashes commonly encountered in multi-template comparative modeling. We benchmarked MTMG on 1,033 sequence alignments generated for CASP9, CASP10 and CASP11 targets, respectively. Using multiple templates with MTMG improves the GDT-TS score and TM-score of structural models by 2.96-6.37% and 2.42-5.19% on the three datasets over using single templates. MTMG's performance was comparable to Modeller in terms of GDT-TS score, TM-score, and GDT-HA score, while the average RMSD was improved by a new sampling approach. The MTMG software is freely available at: http://sysbio.rnet.missouri.edu/multicom_toolbox/mtmg.html.
authors.affiliation: Department of Computer Science, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Jilong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Computer Science, University of Missouri, Columbia, MO 65211, USA.|Informatics Institute, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000465:Algorithms; D020169:Caspases / Q000737:chemistry / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D020407:Internet; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D000072417:Protein Domains; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D015203:Reproducibility of Results; D012984:Software
chemical_list: D007527:Isoenzymes; D011506:Proteins; D020169:Caspases