Molecular Dynamics Simulations in Drug Design

Abstract

This minireview focuses on recent developments in the application of molecular dynamics to drug design. Recent applications of endpoint free-energy computational methods such as molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and generalized Born surface area (MM-GBSA) and linear response methods are described. Recent progress in steered molecular dynamics applied to drug design is reviewed.

Biomolecular recognition of antagonists by α7 nicotinic acetylcholine receptor: Antagonistic mechanism and structure–activity relationships studies

“…The generalized Born method is regarded as a more computationally competent approach to achieving Poisson-Boltzmann like outcomes at lower computational cost, and the relevant relations for the Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) calculation are as follows (Kerrigan, 2013):…”

Investigation on the sucrose binding pocket of HIV-1 Integrase by molecular dynamics and synergy experiments

“…Despite the lack of activity of sucrose in IN in vitro assay, 22 probably due to its high desolvation energy barrier, the numerous interactions established by the ligand at the interface of the two interacting IN monomers prompted us to ask whether this molecule could nevertheless have a kind of modulator effect (stabilization/destabilization) on IN. For this purpose we employed molecular dynamics (MD) simulations and MM-GBSA (Molecular Mechanics-Generalize Born Surface Area) 24 free energy calculations since the good performance of these molecular modeling techniques have been already reported for similar studies on protein-protein interactions. 25 A 4 ns equilibration and a 50 ns production MD simulation with explicit solvent were ran starting from the crystal structure of IN CCD in complex with sucrose (PDB code: 3L3V) and, in parallel, a MD simulation was performed on the apo form of the protein (obtained by removing the sucrose ligand) under the same conditions.…”

Research Techniques Made Simple: Molecular Docking in Dermatology - A Foray into In Silico Drug Discovery

“…Thus, typically only a few (< 1000) molecules would be chosen after docking for subsequent refinement under solute and solvent considerations. These post-docking energy calculations help to increase the true positive rate and are known as molecular mechanics generalized Born molecular surface area and molecular mechanics generalized PoissoneBoltzmann surface area methods, which are reviewed in (Kerrigan, 2013).…”