Importance of protein dynamics in the structure-based drug discovery of class A G protein-coupled receptors (GPCRs)

Demand for novel GPCR modulators is increasing as the association between the GPCR signaling pathway and numerous diseases such as cancers, psychological and metabolic disorders continues to be established. In silico structure-based drug design (SBDD) offers an outlet where researchers could exploit...

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Bibliographic Details
Published in:Current opinion in structural biology 2019-04, Vol.55, p.147-153
Main Authors: Lee, Yoonji, Lazim, Raudah, Macalino, Stephani Joy Y, Choi, Sun
Format: Article
Language:English
Subjects:
Allosteric Site
Drug Design
Drug Discovery
Humans
Ligands
Molecular Docking Simulation - methods
Molecular Dynamics Simulation
Protein Conformation
Receptors, G-Protein-Coupled - chemistry
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Summary:Demand for novel GPCR modulators is increasing as the association between the GPCR signaling pathway and numerous diseases such as cancers, psychological and metabolic disorders continues to be established. In silico structure-based drug design (SBDD) offers an outlet where researchers could exploit the accumulating structural information of GPCR to expedite the process of drug discovery. The coupling of structure-based approaches such as virtual screening and molecular docking with molecular dynamics and/or Monte Carlo simulation aids in reflecting the dynamics of proteins in nature into previously static docking studies, thus enhancing the accuracy of rationally designed ligands. This review will highlight recent computational strategies that incorporate protein flexibility into SBDD of GPCR-targeted ligands.
ISSN:0959-440X
1879-033X
DOI:10.1016/j.sbi.2019.03.015