Unknown

Dataset Information

0

Effects of Water Placement on Predictions of Binding Affinities for p38? MAP Kinase Inhibitors.


ABSTRACT: Monte Carlo free energy perturbation (MC/FEP) calculations have been applied to compute the relative binding affinities of 17 congeneric pyridazo-pyrimidinone inhibitors of the protein p38? MAP kinase. Overall correlation with experiment was found to be modest when the complexes were hydrated using a traditional procedure with a stored solvent box. Significant improvements in accuracy were obtained when the MC/FEP calculations were repeated using initial solvent distributions optimized by the water placement algorithm JAWS. The results underscore the importance of accurate placement of water molecules in a ligand binding site for the reliable prediction of relative free energies of binding.

SUBMITTER: Luccarelli J 

PROVIDER: S-EPMC3029023 | BioStudies | 2010-01-01

REPOSITORIES: biostudies

Similar Datasets

2016-01-01 | S-EPMC6044636 | BioStudies
2010-01-01 | S-EPMC2892976 | BioStudies
2019-01-01 | S-EPMC6615964 | BioStudies
2009-01-01 | S-EPMC2702131 | BioStudies
2012-01-01 | S-EPMC3480999 | BioStudies
2019-01-01 | S-EPMC7932129 | BioStudies
1000-01-01 | S-EPMC5816953 | BioStudies
2006-01-01 | S-EPMC1578458 | BioStudies
2016-01-01 | S-EPMC5777225 | BioStudies
2013-01-01 | S-EPMC4026022 | BioStudies