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 results show correlation with experimentally determined selectivities and provide useful insights into the underlying structural determinants for selectivity.

Assessing protein kinase selectivity with molecular dynamics and MM-PBSA binding free energy calculations / E., Muzzioli; A., Del Rio; Rastelli, Giulio. - In: CHEMICAL BIOLOGY & DRUG DESIGN. - ISSN 1747-0285. - STAMPA. - 78:2(2011), pp. 252-259. [10.1111/j.1747-0285.2011.01140.x]

Assessing protein kinase selectivity with molecular dynamics and MM-PBSA binding free energy calculations.

RASTELLI, Giulio
2011

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 results show correlation with experimentally determined selectivities and provide useful insights into the underlying structural determinants for selectivity.
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Assessing protein kinase selectivity with molecular dynamics and MM-PBSA binding free energy calculations / E., Muzzioli; A., Del Rio; Rastelli, Giulio. - In: CHEMICAL BIOLOGY & DRUG DESIGN. - ISSN 1747-0285. - STAMPA. - 78:2(2011), pp. 252-259. [10.1111/j.1747-0285.2011.01140.x]
E., Muzzioli; A., Del Rio; Rastelli, Giulio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/684300
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