Home > Publications database > Ligand Pose Predictions for Human G Protein-Coupled Receptors: Insights from the Amber-based Hybrid Molecular Mechanics/Coarse-Grained Approach |
Journal Article | FZJ-2020-02855 |
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2020
American Chemical Society64160
Washington, DC
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Please use a persistent id in citations: http://hdl.handle.net/2128/26979 doi:10.1021/acs.jcim.0c00661
Abstract: Human G protein-coupled receptors (hGPCRs) are the most frequent targets of Food and Drug Administration (FDA)-approved drugs. Structural bioinformatics, along with molecular simulation, can support structure-based drug design targeting hGPCRs. In this context, several years ago, we developed a hybrid molecular mechanics (MM)/coarse-grained (CG) approach to predict ligand poses in low-resolution hGPCR models. The approach was based on the GROMOS96 43A1 and PRODRG united-atom force fields for the MM part. Here, we present a new MM/CG implementation using, instead, the Amber 14SB and GAFF all-atom potentials for proteins and ligands, respectively. The new implementation outperforms the previous one, as shown by a variety of applications on models of hGPCR/ligand complexes at different resolutions, and it is also more user-friendly. Thus, it emerges as a useful tool to predict poses in low-resolution models and provides insights into ligand binding similarly to all-atom molecular dynamics, albeit at a lower computational cost.
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