TY  - JOUR
AU  - Schneider, Jakob
AU  - Korshunova, Ksenia
AU  - Si Chaib, Zeineb
AU  - Giorgetti, Alejandro
AU  - Alfonso-Prieto, Mercedes
AU  - Carloni, Paolo
TI  - Ligand Pose Predictions for Human G Protein-Coupled Receptors: Insights from the Amber-based Hybrid Molecular Mechanics/Coarse-Grained Approach
JO  - Journal of chemical information and modeling
VL  - 60
IS  - 10
SN  - 1549-960X
CY  - Washington, DC
PB  - American Chemical Society64160
M1  - FZJ-2020-02855
SP  - 5103–5116
PY  - 2020
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 32786708
UR  - <Go to ISI:>//WOS:000586716900061
DO  - DOI:10.1021/acs.jcim.0c00661
UR  - https://juser.fz-juelich.de/record/878447
ER  -