Exploring human-guided strategies for reaction network exploration: Interactive molecular dynamics in virtual reality as a tool for citizen scientists.

The emerging fields of citizen science and gamification reformulate scientific problems as games or puzzles to be solved. Through engaging the wider non-scientific community, significant breakthroughs may be made by analyzing citizen-gathered data. In parallel, recent advances in virtual reality (VR) technology are increasingly being used within a scientific context and the burgeoning field of interactive molecular dynamics in VR (iMD-VR) allows users to interact with dynamical chemistry simulations in real time. Here, we demonstrate the utility of iMD-VR as a medium for gamification of chemistry research tasks. An iMD-VR "game" was designed to encourage users to explore the reactivity of a particular chemical system, and a cohort of 18 participants was recruited to playtest this game as part of a user study. The reaction game encouraged users to experiment with making chemical reactions between a propyne molecule and an OH radical, and "molecular snapshots" from each game session were then compiled and used to map out reaction pathways. The reaction network generated by users was compared to existing literature networks demonstrating that users in VR capture almost all the important reaction pathways. Further comparisons between humans and an algorithmic method for guiding molecular dynamics show that through using citizen science to explore these kinds of chemical problems, new approaches and strategies start to emerge.

Interactive molecular dynamics in virtual reality from quantum chemistry to drug binding: An open-source multi-person framework.

As molecular scientists have made progress in their ability to engineer nanoscale molecular structure, we face 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 nonintuitive 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, open-source, multiperson 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 potential energy functions, 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 outline how these provide research insight for molecular systems. By synergistically combining human spatial reasoning and design insight with computational automation, technologies such as 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.

Properties of natural double-strand-break sites at a recombination hotspot in Saccharomyces cerevisiae.

This study addresses three questions about the properties of recombination hotspots in Saccharomyces cerevisiae: How much DNA is required for double-strand-break (DSB) site recognition? Do naturally occurring DSB sites compete with each other in meiotic recombination? What role does the sequence located at the sites of DSBs play? In S. cerevisiae, the HIS2 meiotic recombination hotspot displays a high level of gene conversion, a 3'-to-5' conversion gradient, and two DSB sites located approximately 550 bp apart. Previous studies of hotspots, including HIS2, suggest that global chromosome structure plays a significant role in recombination activity, raising the question of how much DNA is sufficient for hotspot activity. We find that 11.5 kbp of the HIS2 region is sufficient to partially restore gene conversion and both DSBs when moved to another yeast chromosome. Using a variety of different constructs, studies of hotspots have indicated that DSB sites compete with one another for DSB formation. The two naturally occurring DSBs at HIS2 afforded us the opportunity to examine whether or not competition occurs between these native DSB sites. Small deletions of DNA at each DSB site affect only that site; analyses of these deletions show no competition occurring in cis or in trans, indicating that DSB formation at each site at HIS2 is independent. These small deletions significantly affect the frequency of DSB formation at the sites, indicating that the DNA sequence located at a DSB site can play an important role in recombination initiation.