Abstract
Understanding how ligands bind to G-protein coupled receptors (GPCRs) provides insights into a myriad of cell processes and is crucial for drug development. Here we extend a hybrid molecular mechanics/coarse-grained (MM/CG) approach applied previously to enzymes to GPCR/ligand complexes. The accuracy of this method for structural predictions is established by comparison with recent atomistic molecular dynamics simulations on the human β2 adrenergic receptor, a member of the GPCRs superfamily. The results obtained with the MM/CG methodology show a good agreement with previous all-atom classical dynamics simulations, in particular in the structural description of the ligand binding site. This approach could be used for high-throughput predictions of ligand poses in a variety of GPCRs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Biomechanical Phenomena
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Humans
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Isoproterenol / chemistry*
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Ligands
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Lipid Bilayers / chemistry*
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Molecular Dynamics Simulation*
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Propanolamines / chemistry*
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Protein Binding
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Protein Structure, Tertiary
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Receptors, Adrenergic, beta-2 / chemistry*
Substances
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Ligands
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Lipid Bilayers
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Propanolamines
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Receptors, Adrenergic, beta-2
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carazolol
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Isoproterenol
Grants and funding
This work has been supported in part by a grant from the Deutsche Forschungsgemeinschaft (CA 973/6-1), by a grant from Vietnam National Foundation for Science and Technology Development (DFG.2011.01), and by a grant from the Project ISS UPR- 20009-1301355 (CUP I85J08000040005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.