title: Capturing native/native like structures with a physico-chemical metric (pcSM) in protein folding.
abstract: Specification of the three dimensional structure of a protein from its amino acid sequence, also called a "Grand Challenge" problem, has eluded a solution for over six decades. A modestly successful strategy has evolved over the last couple of decades based on development of scoring functions (e.g. mimicking free energy) that can capture native or native-like structures from an ensemble of decoys generated as plausible candidates for the native structure. A scoring function must be fast enough in discriminating the native from unfolded/misfolded structures, and requires validation on a large data set(s) to generate sufficient confidence in the score. Here we develop a scoring function called pcSM that detects true native structure in the top 5 with 93% accuracy from an ensemble of candidate structures. If we eliminate the native from ensemble of decoys then pcSM is able to capture near native structure (RMSD<=5Ǻ) in top 10 with 86% accuracy. The parameters considered in pcSM are a C-alpha Euclidean metric, secondary structural propensity, surface areas and an intramolecular energy function. pcSM has been tested on 415 systems consisting 142,698 decoys (public and CASP-largest reported hitherto in literature). The average rank for the native is 2.38, a significant improvement over that existing in literature. In-silico protein structure prediction requires robust scoring technique(s). Therefore, pcSM is easily amenable to integration into a successful protein structure prediction strategy. The tool is freely available at http://www.scfbio-iitd.res.in/software/pcsm.jsp.
authors.affiliation: Kusuma School of Biological Sciences, Indian Institute of Technology, Hauz Khas, New Delhi, India.
authors.forename: Avinash
authors.initials: A
authors.lastname: Mishra
authors.forename: Satyanarayan
authors.initials: S
authors.lastname: Rao
authors.forename: Aditya
authors.initials: A
authors.lastname: Mittal
authors.forename: B
authors.initials: B
authors.lastname: Jayaram
mesh_terms: D000465:Algorithms; D053453:Caspase 9 / Q000737:chemistry*; D020169:Caspases / Q000737:chemistry*; D019295:Computational Biology; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D012984:Software
chemical_list: C099217:CASP5 protein, human; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases