(13b) An Intermittent QM/MM Technique to Model Force Induced Bond Scission in Polymeric Systems

The materials in our bodies are constantly experiencing and responding to external forces on scales both large (e.g. forces impacted on joints and ligaments during exercise) and small (e.g. hydrodynamic shear experienced by proteins and cells). Under such conditions, mechano-chemistry – chemical changes induced by mechanical stimuli – can play a large role in a number of biological processes. These include both events that modify biological function, such as the redox switching behavior of disulfide bonds and instances where a biomolecule assumes a more passive role as a structural material such as actin filaments in muscle or collagen fibers in tendons and other load bearing tissue. Currently, modeling of these single-bond events usually present significant time and size limitations and it is therefore difficult to capture the effect that these small-scale phenomena impart on the large-scale behavior of the material. Modeling these bond-breaking phenomena in the context of their surrounding biomolecular environment has not yet been accomplished, and could allow for the observation of many physiological mechanisms and further exploration of the mechano-chemistry of proteins and protein function. To this end, we have developed a computational workflow that attempts to bridge this gap by using classical molecular dynamics (MD) simulations that are intermittently enhanced on an ad-hoc basis with local quantum calculations using Density Functional based Tight Binding (DFTB). This is accomplished by applying force/ distance cut-offs on load-bearing bonds which trigger the QM/MM calculations to determine whether or not bond scission occurs before switching back to the more computationally efficient MD framework. We demonstrate success on model systems of collagen and sulfide-bond containing proteins and compare these results with experimental measurements. Further refinement and automation of this technique will allow for increases in scale with the goal of creating a multidisciplinary implementation capable of allowing the investigation of problems in fields such as materials science, engineering, and biology.