The Molecular Sciences Software Institute serves as a nexus for science, education, and cooperation serving the worldwide community of computational molecular scientists – a broad field including of biomolecular simulation, quantum chemistry, and materials science. The Institute will spur significant advances in software infrastructure, education, standards, and best-practices that are needed to enable the molecular science community to open new windows on the next generation of scientific Grand Challenges, ranging from the simulation of intrinsically disordered proteins associated with a range of diseases to the design of new catalysts vital to the global chemical industry and climate change. The Institute will help the computational molecular science community to work together to leverage its diverse capabilities that will reduce or eliminate the gulf that currently delays by years the practical realization of theoretical innovations. Ultimately, the Institute will enable computational scientists to tackle problems that are orders of magnitude larger and more complex than those currently within our grasp, and will accelerate the translation of basic science into new technologies essential to the vitality of the economy and environment.
Computational molecular science (CMS), which encompasses the fields of quantum chemistry, materials science, and biomolecular simulation, has achieved fantastic success over its long history. Atomistic and coarse-grained models — ranging from classical molecular dynamics to quantum mechanics and the hierarchy of models in between — have provided unprecedented levels of insight into a wide range of chemical, biological, and soft matter and solid-state phenomena. Such insights have rightly earned the field of CMS its status as “full partner with experiment” in scientific discovery, and today tens of thousands of chemists, biologists, physicists, and geologists worldwide make use of the software the CMS community has produced. However, as these scientists strive globally to address vital questions in their fields, CMS also faces daunting software obstacles — as well as new opportunities. MolSSI’s mission of improving software in the computational molecular sciences will enable researchers to tackle a broad spectrum of scientific challenges. Below are a summary of some of the science that will be enabled through the proposed software advances.
Intrinsically Disordered Proteins
The scientific efforts in the past 30 years have significantly advanced our collective understanding of the folding dynamics and conformational changes present in structured proteins. However, it has long been known that regions of intrinsic disorder are comon in eukaryotic proteins. In fact intrinsically disordered proteins (IDPs) comprise nearly 25% of the human proteome. IPDs are directly associated with numerous human disease such as cancer, cardiovascular disease, amyloidoses, neurodegenerative diseases (e.g. alzheimers) and diabetes. Compared with structured proteins, simulations of IDPs present new computational challenges. More aggressive sampling methods and more accurate force field parameters are required in order to fully characterize the dynamics and functions of these proteins. MolSSI will enable software improvement to overcome the computational efficiency and resource limits of simulating IDPs.
A catalyst is any chemical or biochemical species that enhances the rate of a reaction without being consumed by the reaction (an everyday example being the catalytic converters on cars). A better molecular understanding of catalytic systems will improve existing and emerging technologies for energy production (fuel cells), drug design, biomass conversions and polymeric materials. Current software can simulate limited aspects of catalysts, but not the whole catalytic system. New Hybrid quantum mechanics/molecular mechanics (QM/MM) software must be capable of transparently combining accurate, scalable electronic structure methods with multilayer models, inclusion of environmental effects, and efficient dynamical sampling methods. By developing new software, MolSSI will enable researchers to better understand the mechanisms of catalysts.
Long-range Charge and Excitation Transfer
A wide range of materials and biological systems make use of charge and/or excitation transport over long distances. A particularly engaging example is that of electrochemically active bacteria (EAB). These organisms have been implicated in a range of potential applications including biophotovoltaics, microbial fuel cells, bioremediation of heavy metals and more. However, little is understood on the nature of EAB. In order to understand such complex systems, sophisticated software tools are required that combine models from electronic structure, non-equilibrium dynamics over a range of length scales, and statistical mechanics. While current community codes deploying such models exist, the interoperabilty of such codes are still too primitive to complete the task of understanding EABs. Molssi’s will improve the scalability and compatibility of such codes to handle the computational demands of studying this effect.
(a) Shewanella oneidensis MR-1, an electrochemically-active bacterium exhibiting 8-19 nm nanowires responsible for electron transport (image courtsey of Prof. Ken Nealson). (b) A series of heme cofactors in the protein MtrF illustrating the multi-cytochrome nature of the transport and the molecular structures involved (image is adapted from Breuer, M. et al.).