Exploring the binding mechanism of positive allosteric modulators in human metabotropic glutamate receptor 2 using molecular dynamics simulations

Abstract

Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 2 (mGlu2) is well-known strategy in treatment of psychiatric disorders with the higher selectivity and lower tolerance risk. A mount of PAMs...

A multiple-step screening protocol to identify norepinephrine and dopamine reuptake inhibitors for depression

“…For similar systems with similar ligands or site-directed mutation, the entropy contribution can be omitted if only the relative order of binding affinities is of interest. 43,75…”

“…For similar systems with similar ligands or site-directed mutation, the entropy contribution can be omitted if only the relative order of binding affinities is of interest. 43,75 According to the calculated binding free energies, the ability to bind in two targets for compound 3719810 was comparable. This result was consistent with its binding assays and was also verified by the molecular docking outcome, which indicated that the calculated binding energy effectively reproduced the ascending trend of experimental values.…”

“…All MD simulations were carried out by AMBER20 42 with GPU-accelerated PMEMD, as mentioned in previous studies. 18,[43][44][45] The AMBER force fields for lipid and protein were set as Lipid14 41 and ff14SB, 46 respectively. The ion parameters for TIP3P water were obtained from Joung and Cheatham.…”

Computational molecular interaction between SARS-CoV-2 main protease and theaflavin digallate using free energy perturbation and molecular dynamics

“…Similarly, the conclusion based on single trajectories using a single algorithm can be inaccurate [ 20 ]. Furthermore, binding energy estimation using endpoint methods such as MMGBSA/MMPBSA tends to be less accurate than alchemical free energy calculation [ 63 , 64 ]. In the case of the main protease inhibitor discovery, free energy perturbation is recommended in benchmarking studies [ 16 , 17 ].…”

CHARMM-GUI Membrane Builder: Past, Current, and Future Developments and Applications

“…Another important aspect about the ion channel is drug binding. MD simulations are used to explore ligand binding stability and to better assess the induced-fit effect from docking results , or to verify the binding poses from structural biology works. , Ligand-binding free energy calculations yield a quantitative profile for comparison with experimental measurements . In addition, the dynamical effects exerted by ligands can be accessed from simulation trajectories.…”