Combining Virtual Reality Visualization with Ensemble Molecular Dynamics to Study Complex Protein Conformational Changes.

Molecular dynamics (MD) simulations are increasingly used to elucidate relationships between protein structure, dynamics, and their biological function. Currently, it is extremely challenging to perform MD simulations of large-scale structural rearrangements in proteins that occur on millisecond timescales or beyond, as this requires very significant computational resources, or the use of cumbersome "collective variable" enhanced sampling protocols. Here, we describe a framework that combines ensemble MD simulations and virtual reality visualization (eMD-VR) to enable users to interactively generate realistic descriptions of large amplitude, millisecond timescale protein conformational changes in proteins. Detailed tests demonstrate that eMD-VR substantially decreases the computational cost of folding simulations of a WW domain, without the need to define collective variables a priori. We further show that eMD-VR generated pathways can be combined with Markov state models to describe the thermodynamics and kinetics of large-scale loop motions in the enzyme cyclophilin A. Our results suggest eMD-VR is a powerful tool for exploring protein energy landscapes in bioengineering efforts.

Sampling molecular conformations and dynamics in a multiuser virtual reality framework.

We describe a framework for interactive molecular dynamics in a multiuser virtual reality (VR) environment, combining rigorous cloud-mounted atomistic physics simulations with commodity VR 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, in which 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 modeling tasks more quickly than they can using conventional interfaces, especially for molecular pathways and structural transitions whose conformational choreographies are intrinsically three-dimensional. This framework should accelerate progress in nanoscale molecular engineering areas including conformational mapping, drug development, synthetic biology, and catalyst design. More broadly, our findings highlight the potential of VR in scientific domains where three-dimensional dynamics matter, spanning research and education.

Experimental and modeling studies of B atom number density distributions in hot filament activated B2H6/H2 and B2H6/CH4/H2 gas mixtures.

Experimental and modeling studies of the gas-phase chemistry occurring in dilute, hot filament (HF) activated B2H6/H2 and B2H6/CH4/H2 gas mixtures are reported. Spatially resolved relative number densities of B (and H) atoms have been measured by resonance enhanced multiphoton ionization methods, as a function of process conditions (e.g. the HF material and its temperature, the B2H6/H2 mixing ratio, and the presence (or not) of added CH4). Three-dimensional modeling of the H/B chemistry prevailing in such HF activated gas mixtures using a simplified representation of the gas phase chemistry succeeds in reproducing all of the experimentally observed trends, and in illustrating the key role of the "H-shifting" reactions BHx + H <= => BHx-1 + H2 (x = 1-3) in enabling rapid interconversion between the various BHx (x = 0-3) species. CH4 addition, at partial pressures appropriate for growth of boron-doped diamond by chemical vapor deposition methods, leads to approximately 30% reduction in the measured B atom signal near the HF. The modeling suggests that this is mainly due to concomitant H atom depletion near the HF, but it also allows us a first assessment of the possible contributions from B/C coupling reactions upon CH4 addition to HF activated B2H6/H2 gas mixtures.

Early environment, emotions, responses to stress, and health.

A harsh early family environment is related to mental and physical health in adulthood. An important question is why family environment in childhood is associated with these outcomes so long after its initial occurrence. We describe a program of research that evaluates a model linking these variables to each other. Specifically, we hypothesize that low social competence and negative emotional states may mediate relations between a harsh early family environment and physiological/neuroendocrine responses to stress, as well as long-term health outcomes. We report evidence that the model characterizes self-rated health, cortisol responses to stress, and, in males only, elevated cardiovascular responses to stress. We discuss how the social context of early life (such as SES) may affect the family environment in ways that precipitate adverse health consequences. Perspectives on comorbidities in physical and mental health are discussed.

Are self-enhancing cognitions associated with healthy or unhealthy biological profiles?

Self-enhancement is variously portrayed as a positive illusion that can foster health and longevity or as defensive neuroticism that can have physiological-neuroendocrine costs. In a laboratory stress-challenge paradigm, the authors found that high self-enhancers had lower cardiovascular responses to stress, more rapid cardiovascular recovery, and lower baseline cortisol levels, consistent with the positive illusions predictions and counter to the predictions of the defensive neuroticism position. A second set of analyses, replicating the "illusory mental health paradigm" (J. Shedler, M. Mayman, & M. Manis, 1993), also did not support the defensive neuroticism hypothesis. The association between self-enhancement and cortisol was mediated by psychological resources; analyses of the cardiovascular results provided no definitive mediational pathway. Discussion centers on the potential stress-buffering effects of self-enhancing beliefs.

Portrait of the self-enhancer: well adjusted and well liked or maladjusted and friendless?

Research has variously portrayed self-enhancement as an indicator of narcissistic defensiveness or as a concomitant of mental health. To address this controversy, the present study used multiple measures of self-enhancement along with multiple measures and judges of mental health, comprehensively assessing their relationship. The results indicated that self-enhancement is positively associated with multiple indicators of mental health and with a more favorable impact on others. Discussion centers on a reconciliation of discrepant portraits of the self-enhancer.