Recent advances in computational resources have allowed Molecular Dynamics (MD) to be run in real-time and displayed using Virtual Reality (VR), creating a fully interactive and immersive experience. Narupa is an open source program for performing Interactive Molecular Dynamics in Virtual Reality (iMD-VR), which is shown to have benefits for performing complex molecular manipulation tasks (in comparison to more conventional interfaces). Here, it is applied to the study of protein-ligand systems, starting with an initial exploration of three protein targets of varying complexity, and later expanded towards a target of high pharmacological relevance (SARS-CoV-2 Mpro). iMD-VR is demonstrated to be a useful tool for complexing proteins to both small, drug-like molecules and larger, more rotationally complex oligopeptides. Sound is also explored as a mechanism for providing feedback during iMD-VR about information relevant to ligand docking, where audio cues indicate the formation of key hydrogen bonding interactions to a user. Furthermore, the utility of iMD-VR is explored as a tool for enhancing the rate of sampling in a chemical system: the free energies of a series of distinct unbinding pathways,which were quickly generated using iMD-VR, are estimated using Umbrella Sampling. Chiefly, an iMD-VR unbinding pathway can be used to quickly describe a route in reduced dimensional space to bias sampling along. Overall, this thesis explores the utility of using iMD-VR for understanding protein-ligand systems, from recreating experimental (crystallographic) protein-ligand structures, to novel ways of conveying key simulation data, to quickly generating unbinding pathways which can be used to guide biased sampling methods. iMD-VR shows great promise as a tool for studying chemical systems of pharmacological interest.
- Interactive Molecular Dynamics
- Virtual Reality
- Drug design
- Molecular Dynamics