%0 Journal Article
%A Schneider, Jakob
%A Korshunova, Ksenia
%A Si Chaib, Zeineb
%A Giorgetti, Alejandro
%A Alfonso-Prieto, Mercedes
%A Carloni, Paolo
%T Ligand Pose Predictions for Human G Protein-Coupled Receptors: Insights from the Amber-based Hybrid Molecular Mechanics/Coarse-Grained Approach
%J Journal of chemical information and modeling
%V 60
%N 10
%@ 1549-960X
%C Washington, DC
%I American Chemical Society64160
%M FZJ-2020-02855
%P 5103–5116
%D 2020
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ 32786708
%U <Go to ISI:>//WOS:000586716900061
%R 10.1021/acs.jcim.0c00661
%U https://juser.fz-juelich.de/record/878447