Development of non-equilibrium computer simulations of molecular motors

While ubiquitous molecular dynamics (MD) simulations generate movies of proteins dancing around in space, the simulated motion depicts the equilibrium dance of dead molecules rather than the nonequilibrium dynamics of a living system. To bring a molecular machine to life, it must consume a fuel that powers that nonequilibrium motion, the type of motion that allows muscles to contract, DNA to accurately replicate, and neurons to compute. Despite the importance of these nonequilibrium scenarios, almost all theoretical and computational tools are limited to equilibrium situations. The proposed project will build upon initial proof of concept work to simulate the mechanical motion of motors subjected to nonequilibrium chemistry. The initial product will be simulation methods and code that are shared with the broader community. We aim to subsequently use those simulations, complemented by experiments, to identify molecular structures that yield effective molecular motors. For example, suppose one desires a molecular motor that walks along a fiber by using adenosine triphosphate (ATP) as a fuel. Designing a molecular structure for such a motor, requires a mechanistic understanding of how the function arises from structure in the nonequilibrium operating regime, something our nonequilibrium simulations will be uniquely positioned to provide. We will build upon an initial “toy model” illustration to ultimately prescribe designs for new synthetic molecular motors and for beneficial mutations in natural protein motors.