A simplified homology-model builder toward highly protein-like structures: an inspection of restraining potentials

J Comput Chem. 2012 Sep 15;33(24):1927-35. doi: 10.1002/jcc.23024. Epub 2012 May 30.

Abstract

A homology model builder using simple restraining potentials based on spline-interpolated quadratic functions is developed and interfaced with CHARMM package. The continuity and stability of the potential function were validated, and the parameters were optimized using the CASP7 targets. The performance of the model builder was benchmarked to the Modeller program using the template-based modeling targets in CASP9. The benchmark results show that, while our builder yields the structures with slightly lower packing, backbone, and template modeling scores, our models show much better protein-like scores in terms of normalized discrete optimized protein energy, dipolar distance-scaled finite-ideal gas reference, Molprobity clash, Ramachandran appearance Z-score, and rotamer Z-score. As our model builder is interfaced with CHARMM, it is advantageous to directly use other CHARMM functionality and energy functions to refine the model structures or to use the models for other computational studies using CHARMM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Caspase 7 / chemistry*
  • Caspase 9 / chemistry*
  • Databases, Protein
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Proteomics / methods*
  • Sequence Homology, Amino Acid*
  • Software*
  • Thermodynamics

Substances

  • CASP7 protein, human
  • CASP9 protein, human
  • Caspase 7
  • Caspase 9