Binding free energy calculation with QM/MM hybrid methods for Abl-Kinase inhibitor.

ABSTRACT: We report a Quantum mechanics/Molecular Mechanics-Poisson-Boltzmann/ Surface Area (QM/MM-PB/SA) method to calculate the binding free energy of c-Abl human tyrosine kinase by combining the QM and MM principles where the ligand is treated quantum mechanically and the rest of the receptor by classical molecular mechanics. To study the role of entropy and the flexibility of the protein ligand complex in a solvated environment, molecular dynamics calculations are performed using a hybrid QM/MM approach. This work shows that the results of the QM/MM approach are strongly correlated with the binding affinity. The QM/MM interaction energy in our reported study confirms the importance of electronic and polarization contributions, which are often neglected in classical MM-PB/SA calculations. Moreove

SUBMITTER: Dubey KD 

PROVIDER: S-EPMC3006460 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature