Recent Developments and Applications of the MMPBSA Method

Abstract

The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) approach has been widely applied as an efficient and reliable free energy simulation method to model molecular recognition, such as for protein-ligand binding interactions. In this review, we focus on recent developments and applications of the MMPBSA method. The methodology review covers solvation terms, the entropy term, extensions to membrane proteins and high-speed screening, and new automation toolkits. Recent applications in various important biomedical and chemical fields are also reviewed. We conclude with a few future directions aimed at making MMPBSA a more robust and efficient method.

Computer-aided synthesis of dapsone-phytochemical conjugates against dapsone-resistant Mycobacterium leprae

“…All-atom molecular dynamics simulation study. The dynamic behaviours of each MlDHPS DDS/ DPCs complex was investigated using all-atom molecular dynamics simulations using Amber-99sb ILDN force field in TIP3 water models employed in GROMACSv5.1 1,[17][18][19] . A three-step approach was employed for simulation studies, which include heating the system followed by equilibration and at the last the production run at 300 K for 40 ns for each system.…”

“…Gromacs utility tools were employed for trajectory analysis. The quality assurance parameters like backbone RMSD, C-alpha root mean square fluctuations, a radius of gyration and intermolecular hydrogen bonds were computed using gmx rms, gmx rmsf, gmx gyrate, and gmx hbond utility toolkits of GROMACS 17,18 . Two-dimensional graphs depicting the dynamic stability were plotted using the Xmgrace tool.…”

Deciphering the ‘Elixir of Life’: Dynamic Perspectives into the Allosteric Modulation of Mitochondrial ATP Synthase by J147, a Novel Drug in the Treatment of Alzheimer's Disease

“…This was done in order to considerably reduce or eliminate entropic effects on the binding energy of J147. [35][36][37] However, even though it is able to estimate the binding profiles of ligands to proteins, it is important to mention that MM/PBSA-based energy approximations are affected intrinsically by large uncertainties. [35][36][37]…”

Molecular docking and simulation study for synthesis of alternative dapsone derivative as a newer antileprosy drug in multidrug therapy

“…27,28 To understand the energetic force that drives the MlDHPSs-dapsone/DDs interactions and ascertain the central forces of the binding affinity, binding free energies were performed using MM/ PBSA method. Nevertheless, using these simple scoring functions used in docking programs often neglects the significant energetic contributions (solvation free energy), which may not be consistent for the prediction of the binding pose and binding affinity of a molecule.…”

“…This method is often a choice for efficient and reliable free energy calculation tool for the molecular recognition process. 27,28 To understand the energetic force that drives the MlDHPSs-dapsone/DDs interactions and ascertain the central forces of the binding affinity, binding free energies were performed using MM/ PBSA method. The energy components E MM , G polar , and | 9847 G nonpolar of each complex were estimated for 1000 snapshots extracted at equal interval from all 40 ns production trajectories of the MlDHPS-DD3/dapsone complexes.…”