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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., Comment: PLOS ONE

As molecular scientists have made progress in their ability to engineer nano-scale molecular structure, we are facing new challenges in our ability to engineer molecular dynamics (MD) and flexibility. Dynamics at the molecular scale differs from the familiar mechanics of everyday objects, because it involves a complicated, highly correlated, and three-dimensional many-body dynamical choreography which is often non-intuitive even for highly trained researchers. We recently described how interactive molecular dynamics in virtual reality (iMD-VR) can help to meet this challenge, enabling researchers to manipulate real-time MD simulations of flexible structures in 3D. In this article, we outline efforts to extend immersive technologies to the molecular sciences, and we introduce 'Narupa', a flexible, open-source, multi-person iMD-VR software framework which enables groups of researchers to simultaneously cohabit real-time simulation environments to interactively visualize and manipulate the dynamics of molecular structures with atomic-level precision. We outline several application domains where iMD-VR is facilitating research, communication, and creative approaches within the molecular sciences, including training machines to learn reactive potential energy surfaces (PESs), biomolecular conformational sampling, protein-ligand binding, reaction discovery using 'on-the-fly' quantum chemistry, and transport dynamics in materials. We touch on iMD-VR's various cognitive and perceptual affordances, and how these provide research insight for molecular systems. By synergistically combining human spatial reasoning and design insight with computational automation, technologies like iMD-VR have the potential to improve our ability to understand, engineer, and communicate microscopic dynamical behavior, offering the potential to usher in a new paradigm for engineering molecules and nano-architectures.

In most VR experiences, the visual sense dominates other modes of sensory input, encouraging non-visual senses to respond as if the visual were real. The simulated visual world thus becomes a sort of felt actuality, where the 'actual' physical body and environment can 'drop away', opening up possibilities for designing entirely new kinds of experience. Most VR experiences place visual sensory input (of the simulated environment) in the perceptual foreground, and the physical body in the background. In what follows, we discuss methods for resolving the apparent tension which arises from VR's prioritization of visual perception. We specifically aim to understand how somatic techniques encouraging participants to 'attend to their attention' enable them to access more subtle aspects of sensory phenomena in a VR experience, bound neither by rigid definitions of vision-based virtuality nor body-based corporeality. During a series of workshops, we implemented experimental somatic-dance practices to better understand perceptual and imaginative subtleties that arise for participants whilst they are embedded in a multi-person VR framework. Our preliminary observations suggest that somatic methods can be used to design VR experiences which enable (i) a tactile quality or felt sense of phenomena in the virtual environment (VE), (ii) lingering impacts on participant imagination even after the VR headset is taken off, and (iii) an expansion of imaginative potential.

We describe a framework for interactive molecular dynamics in a multiuser virtual reality environment, combining rigorous cloud-mounted physical atomistic simulation with commodity virtual reality hardware, which we have made accessible to readers (see isci.itch.io/nsb-imd). It allows users to visualize and sample, with atomic-level precision, the structures and dynamics of complex molecular structures 'on the fly', and to interact with other users in the same virtual environment. A series of controlled studies, wherein participants were tasked with a range of molecular manipulation goals (threading methane through a nanotube, changing helical screw-sense, and tying a protein knot), quantitatively demonstrate that users within the interactive VR environment can complete sophisticated molecular modelling tasks more quickly than they can using conventional interfaces, especially for molecular pathways and structural transitions whose conformational choreographies are intrinsically 3d. This framework should accelerate progress in nanoscale molecular engineering areas such as drug development, synthetic biology, and catalyst design. More broadly, our findings highlight VR's potential in scientific domains where 3d dynamics matter, spanning research and education., Comment: 5 pages, 3 figures, 19 pages Supporting Info