Capturing native/native like structures with a physico-chemical metric (pcSM) in protein folding

Biochim Biophys Acta. 2013 Aug;1834(8):1520-31. doi: 10.1016/j.bbapap.2013.04.023. Epub 2013 May 7.


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

MeSH terms

  • Algorithms
  • Caspase 9 / chemistry*
  • Caspases / chemistry*
  • Computational Biology*
  • Computer Simulation
  • Humans
  • Models, Molecular
  • Protein Conformation
  • Protein Folding*
  • Software*


  • CASP5 protein, human
  • CASP9 protein, human
  • Caspase 9
  • Caspases