Paper Info
Title
Accurate and efficient generalized born model based on solvent accessibility: derivation and application for LogP octanol/water prediction and flexible peptide docking.
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 Angstrom(-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 Angstrom to the X-ray structure. (C) 2004 Wiley Periodicals, Inc.
Year
DOI
Venue
2004
10.1002/jcc.10392
JOURNAL OF COMPUTATIONAL CHEMISTRY
Keywords
Field
DocType
generalized Born model,solvent accessiblity,LogP octanol/water prediction,peptide docking
Electrostatics,Octanol,Correlation coefficient,Monte Carlo method,Molecule,Computational chemistry,Chemistry,Atom,Boundary element method,Solvation
Journal
Volume
Issue
ISSN
25
4
0192-8651
Citations 
PageRank 
References 
5
0.98
5
Authors
1
Name
Order
Citations
PageRank
Maxim Totrov126931.59