Найдено научных статей и публикаций: 1, для научной тематики: Alanine-mutagenesis . MM-PBSA method . Molecular Dynamics Simulations . Protein-hydration . Salt-bridge
1.
Kshatresh Dutta Dubey and Rajendra Prasad Ojha
- Journal of Molecular Modeling , 2012
Abl kinase plays a decisive role in the mechanism
of the most fatal human pathogen chronic mylogenous leukemia (CML). Here, we have carried out a comprehensive study about the conformational flexibility, role of salt bridge and the protein- ligand interaction for this kinase with its well-known inhi...
Abl kinase plays a decisive role in the mechanism
of the most fatal human pathogen chronic mylogenous leukemia (CML). Here, we have carried out a comprehensive study about the conformational flexibility, role of salt bridge and the protein- ligand interaction for this kinase with its well-known inhibitor, Imatinib. We have performed molecular dynamics simulations for conformational behavior, investigated the salt bridges and calculated the binding free energy of Imatinib with MM-PB/SA method for Abl kinase complex. We also explored the role of salt-bridge in the kinase complex and its effect on binding activity of inhibitors. Furthermore, to investigate the importance of those residues which form salt bridges, we mutated them by Alanine with the help of Alanine scanning program. We noticed significant variations in total free energy of Imatinib in all possible mutations. The binding free energy of ligand for kinase receptor was analyzed by molecular mechanics Poission Boltzmann surface area (MM-PB/SA) method. These results suggest that conserved glutamic acid and lysine are necessary for stability of complex.