Interactive molecular dynamics in virtual reality for accurate flexible protein-ligand docking

• DOI: 10.1371/journal.pone.0228461
• Publication Date: 2020-03-11T17:26:35Z
• Authors: Helen M. Deeks; Rebecca K. Walters; Stephanie R. Hare; Michael B. O’Connor; Adrian J. Mulholland; David R. Glowacki
• Keywords: DOCK; Docking (animal)

Simulating drug binding and unbinding is a challenge, as the rugged energy landscapes that separate bound unbound states require extensive sampling consumes significant computational resources. Here, we describe use of interactive molecular dynamics in virtual reality (iMD-VR) an accurate low-cost strategy for flexible protein-ligand docking. We outline experimental protocol which enables expert iMD-VR users to guide ligands into out pockets trypsin, neuraminidase, HIV-1 protease, recreate their respective crystallographic poses within 5 - 10 minutes. Following brief training phase, our studies shown novices were able generate rebinding pathways on similar timescales experts, with majority recover 2.15 Angstrom RMSD pose. These results indicate affords sufficient control carry detailed atomic manipulations required dock dynamic enzyme active sites poses, offering interesting new approach simulating docking generating hypotheses.