Abstract / Description of output
An efficient molecular simulation methodology has been developed to determine the positioning of water molecules in the binding site of a protein or protein-ligand complex. Occupancies and absolute binding free energies of water Molecules are computed using a statistical thermodynamics approach. The methodology, referred to as Just Add Water Molecules (JAWS), features "theta-water" molecules that can appear and disappear on a binding-site grid. Key approximations render the technique far more efficient than conventional free energy simulations. Testing of JAWS oil five diverse examples (neuraminidase, scytalone dehydratase, major Urinary protein 1, beta-lactoglobulin, and COX-2) demonstrates its accuracy in locating hydration sites in comparison to results from high-resolution crystal Structures. Possible applications include aid in refinement of protein crystal structures, drug lead Optimization, setup of docking calculations, and simulations of protein-ligand complexes.
Original language | English |
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Pages (from-to) | 13337-13346 |
Number of pages | 10 |
Journal | Journal of Physical Chemistry B (Soft Condensed Matter and Biophysical Chemistry) |
Volume | 113 |
Issue number | 40 |
DOIs | |
Publication status | Published - 8 Oct 2009 |