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- Title
Assessing Protein Kinase Selectivity with Molecular Dynamics and MM-PBSA Binding Free Energy Calculations.
- Authors
Muzzioli, Elena; Del Rio, Alberto; Rastelli, Giulio
- Abstract
An application of molecular dynamics and molecular mechanics Poisson–Boltzmann surface area techniques to the prediction of protein kinase inhibitor selectivity is presented. A highly active and selective ERK2 inhibitor was placed in equivalent orientations in five different protein kinases (SRC, LCK, GSK3, JNK3 and Aurora-A). Binding free energies were then computed with the molecular mechanics Poisson–Boltzmann surface area approach using 15 nanosecond fully solvated molecular dynamics trajectories of the corresponding protein-ligand complexes. The resultsshow correlation with experimentally determined selectivities and provide useful insights into the underlying structural determinants for selectivity.
- Subjects
PROTEIN kinases; PROTEIN binding; MOLECULAR dynamics; ADENOSINE triphosphate; LIGANDS (Biochemistry); CHEMICAL biology
- Publication
Chemical Biology & Drug Design, 2011, Vol 78, Issue 2, p252
- ISSN
1747-0277
- Publication type
Article
- DOI
10.1111/j.1747-0285.2011.01140.x