Interactive molecular dynamics in virtual reality for accurate flexible protein-ligand docking
| Autor: | Stephanie R. Hare, Michael B. O'Connor, Adrian J. Mulholland, David R. Glowacki, Rebecca K. Walters, Helen M. Deeks |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_treatment
Social Sciences Plasma protein binding Crystal structure Pathology and Laboratory Medicine Biochemistry Physical Chemistry 01 natural sciences Molecular dynamics Immunodeficiency Viruses Human–computer interaction Aspartic acid Biochemical Simulations Psychology Amino Acids chemistry.chemical_classification Sulfonamides 0303 health sciences 010304 chemical physics Organic Compounds Computational Physics (physics.comp-ph) Biological Physics (physics.bio-ph) Medical Microbiology Viral Pathogens Physical Sciences physics.bio-ph Medicine Physics - Computational Physics Science Virtual reality Microbiology 03 medical and health sciences Oseltamivir Binding site Microbial Pathogens Protease Ligand Organisms Chemical Compounds Biology and Life Sciences Proteins Computational Biology Benzamidines chemistry Docking (molecular) physics.comp-ph FOS: Biological sciences HIV-1 Carbamates RNA viruses Computer science Molecular Dynamics Ligands Drug Users Computational Chemistry HIV Protease Medicine and Health Sciences Trypsin Zanamivir Multidisciplinary Hydrogen bond Acidic Amino Acids Virtual Reality Proteases Enzymes Addicts Chemistry Viruses Pathogens Research Article Protein Binding FOS: Physical sciences Addiction Neuraminidase Molecular Dynamics Simulation q-bio.BM DOCK Retroviruses 0103 physical sciences medicine Physics - Biological Physics Furans 030304 developmental biology Aspartic Acid Binding Sites Chemical Bonding Lentivirus Organic Chemistry HIV Biomolecules (q-bio.BM) Hydrogen Bonding Enzyme Protein–ligand docking Quantitative Biology - Biomolecules Enzymology Serine Proteases |
| Zdroj: | Deeks, H M, Walters, R K, Hare, S R, O’Connor, M B, Mulholland, A J & Glowacki, D R 2020, ' Interactive molecular dynamics in virtual reality for accurate flexible protein-ligand docking ', PLoS ONE, vol. 15, no. 3, e0228461 . https://doi.org/10.1371/journal.pone.0228461 PLoS ONE PLoS ONE, Vol 15, Iss 3, p e0228461 (2020) |
| Popis: | Simulating drug binding and unbinding is a challenge, as the rugged energy landscapes that separate bound and unbound states require extensive sampling that consumes significant computational resources. Here, we describe the use of interactive molecular dynamics in virtual reality (iMD-VR) as an accurate low-cost strategy for flexible protein-ligand docking. We outline an experimental protocol which enables expert iMD-VR users to guide ligands into and out of the binding pockets of trypsin, neuraminidase, and HIV-1 protease, and recreate their respective crystallographic protein-ligand binding poses within 5 - 10 minutes. Following a brief training phase, our studies shown that iMD-VR novices were able to generate unbinding and rebinding pathways on similar timescales as iMD-VR experts, with the majority able to recover binding poses within 2.15 Angstrom RMSD of the crystallographic binding pose. These results indicate that iMD-VR affords sufficient control for users to carry out the detailed atomic manipulations required to dock flexible ligands into dynamic enzyme active sites and recover crystallographic poses, offering an interesting new approach for simulating drug docking and generating binding hypotheses. PLOS ONE |
| Databáze: | OpenAIRE |
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