Chapter title |
Molecular Basis of Ligand Dissociation from G Protein-Coupled Receptors and Predicting Residence Time
|
---|---|
Chapter number | 9 |
Book title |
Computational Methods for GPCR Drug Discovery
|
Published in |
Methods in molecular biology, January 2018
|
DOI | 10.1007/978-1-4939-7465-8_9 |
Pubmed ID | |
Book ISBNs |
978-1-4939-7464-1, 978-1-4939-7465-8
|
Authors |
Dong Guo, Adriaan P. IJzerman |
Abstract |
G protein-coupled receptors (GPCRs) are integral membrane proteins and represent the largest class of drug targets. During the past decades progress in structural biology has enabled the crystallographic elucidation of the architecture of these important macromolecules. It also provided atomic-level visualization of ligand-receptor interactions, dramatically boosting the impact of structure-based approaches in drug discovery. However, knowledge obtained through crystallography is limited to static structural information. Less information is available showing how a ligand associates with or dissociates from a given receptor, whose importance is in fact increasingly recognized by the drug research community. Owing to recent advances in computer power and algorithms, molecular dynamics stimulations have become feasible that help in analyzing the kinetics of the ligand binding process. Here, we review what is currently known about the dynamics of GPCRs in the context of ligand association and dissociation, as determined through both crystallography and computer simulations. We particularly focus on the molecular basis of ligand dissociation from GPCRs and provide case studies that predict ligand dissociation pathways and residence time. |
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United States | 1 | 100% |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
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Unknown | 20 | 100% |
Demographic breakdown
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Student > Ph. D. Student | 6 | 30% |
Researcher | 4 | 20% |
Student > Doctoral Student | 2 | 10% |
Student > Master | 2 | 10% |
Student > Bachelor | 1 | 5% |
Other | 1 | 5% |
Unknown | 4 | 20% |
Readers by discipline | Count | As % |
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Chemistry | 4 | 20% |
Agricultural and Biological Sciences | 3 | 15% |
Biochemistry, Genetics and Molecular Biology | 2 | 10% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
Psychology | 1 | 5% |
Other | 3 | 15% |
Unknown | 6 | 30% |