Blog
About

  • Record: found
  • Abstract: found
  • Article: not found

Accurate and efficient generalized born model based on solvent accessibility: derivation and application for LogP octanol/water prediction and flexible peptide docking.

Journal of Computational Chemistry

chemistry, Water, Thermodynamics, Static Electricity, Solvents, Protein Folding, Peptides, Octanols, Models, Molecular, Computer Simulation, Algorithms

Read this article at

ScienceOpenPublisherPubMed
Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      A novel method for fast and accurate evaluation of the generalized Born radii in macromolecular solvation electrostatics calculations is proposed, based on the solvent accessibility of the first two solvation layers around an atom. The reverse generalized Born radii calculated by the method have correlation coefficient of 98.7% and RMSD of 0.031 A(-1) with the values obtained using a precise but significantly slower numerical boundary element solution. The method is applied to derive an estimate of the free solvation energy difference between octanol and water and to predict LogP octanol-water. A nine-parameter model is optimized on an 81 compound training set and applied to predict LogP(ow) for an external evaluation set of 19 drug molecules with RMSD of 0.9. The new GB approximation is also tested in Monte Carlo docking simulations of the fully flexible p53 peptide fragment to MDM2. The best energy solution found in the simulations has RMSD of 2.8 A to the X-ray structure. Copyright 2004 Wiley Periodicals, Inc. J Comput Chem 25: 609-619, 2004

      Related collections

      Author and article information

      Journal
      10.1002/jcc.10392
      14735578

      Comments

      Comment on this article