Free energy methods commonly in use, utilize equilibrium approaches which maintain a Boltzmann distribution of conformations throughout the simulation. Enhanced sampling methods such as Asynchronous replica-exchange (AsyncRE) allow these calculations to achieve faster convergence through exchanging information between simulation threads. However, these exchanges are difficult to happen on computational grids and large heterogeneous computational clusters because of inefficient communication between threads. The non-equilibrium formulation based on the Jarzynski relationship between free energy and work value is an effective alternative in this context as simulation threads running calculation in non-equilibrium by applying this relationship do not require communicating with each other. We will review our present and ongoing work on the implementation of non-equilibrium thermodynamic approaches combined with an alchemical single-decoupling method (SDM) implementation to calculate binding free energies of protein-ligand complexes. We will present results indicating that, though somewhat less efficient compared to equilibrium methods, our implementation of the non-equilibrium approach leads to efficient utilization of heterogeneous computing environments.<br/><br/>

Non-equilibrium alchemical molecular dynamics simulations of protein-ligand binding

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.