Analysis of Biomolecular Solvation Sites by 3D-RISM Theory
- 29 May 2013
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Physical Chemistry B
- Vol. 117 (22), 6718-6723
- https://doi.org/10.1021/jp4046116
Abstract
We derive, implement, and apply equilibrium solvation site analysis for biomolecules. Our method utilizes 3D-RISM calculations to quickly obtain equilibrium solvent distributions without either necessity of simulation or limits of solvent sampling. Our analysis of these distributions extracts highest likelihood poses of solvent as well as localized entropies, enthalpies, and solvation free energies. We demonstrate our method on a structure of HIV-1 protease where excellent structural and thermodynamic data are available for comparison. Our results, obtained within minutes, show systematic agreement with available experimental data. Further, our results are in good agreement with established simulation-based solvent analysis methods. This method can be used not only for visual analysis of active site solvation but also for virtual screening methods and experimental refinement.Keywords
This publication has 36 references indexed in Scilit:
- Grid inhomogeneous solvation theory: Hydration structure and thermodynamics of the miniature receptor cucurbit[7]urilThe Journal of Chemical Physics, 2012
- Let’s get honest about samplingJournal of Computer-Aided Molecular Design, 2011
- Effects of Water Placement on Predictions of Binding Affinities for p38α MAP Kinase InhibitorsJournal of Chemical Theory and Computation, 2010
- Prediction of protein–ligand binding affinity by free energy simulations: assumptions, pitfalls and expectationsJournal of Computer-Aided Molecular Design, 2010
- Computation of binding free energy with molecular dynamics and grand canonical Monte Carlo simulationsThe Journal of Chemical Physics, 2008
- Role of the Active-Site Solvent in the Thermodynamics of Factor Xa Ligand BindingJournal of the American Chemical Society, 2008
- Motifs for molecular recognition exploiting hydrophobic enclosure in protein–ligand bindingProceedings of the National Academy of Sciences of the United States of America, 2007
- Inhomogeneous Fluid Approach to Solvation Thermodynamics. 2. Applications to Simple FluidsThe Journal of Physical Chemistry B, 1998
- Inhomogeneous Fluid Approach to Solvation Thermodynamics. 1. TheoryThe Journal of Physical Chemistry B, 1998
- An Integral Equation To Describe the Solvation of Polar Molecules in Liquid WaterThe Journal of Physical Chemistry B, 1997