VR combined with cloud computing enables surgical manipulation of real-time molecular simulations, accelerating 3D research tasks.

The main protease (Mpro) of SARS-CoV-2 is central to viral maturation and is a promising drug target, but little is known about structural aspects of how it binds to its...

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 threedimensional 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 various efforts to extend immersive technologies to the molecular sciences, and we introduce 'Narupa', a flexible, opensource, multi-person iMD-VR software framework which enables groups of researchers to simultaneously cohabit realtime 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.

The reemergence of virtual reality (VR) in the past few years has led to affordable, high-quality commodity hardware that can offer new ways to teach, communicate, and engage with complex concepts. In a higher-education context, these immersive technologies make it possible to teach complex molecular topics in a way that may aid or even supersede traditional approaches such as molecular models, textbook images, and traditional screen-based computational environments. In this work we describe a study involving 22 third-year UK undergraduate chemistry students who undertook a traditional computational chemistry class complemented by an additional component which we designed to utilize real-time interactive molecular dynamics simulations in VR (iMD-VR). Exploiting the flexibility of an open-source iMD-VR framework which we recently described, the students were given three short tasks to complete in iMD-VR: (1) interactive rearrangement of the chorismate molecule to prephenate using forces obtained from density functional theory calculations; (2) unbinding of chorismate from the active site chorismate mutase enzyme using molecular mechanics forces calculated in real-time; and (3) docking of chorismate with chorismate mutase using real-time molecular mechanics forces. A student survey indicated that most students found the iMD-VR component more engaging than the traditional approach, and also that it improved their perceived educational outcomes and their interest in continuing on in the field of computational sciences.

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 Å 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.