(525g) Non-Equilibrium Simulations As a Tool to Obtain Equilibrium Properties of Biomolecular Systems

Free energy is an essential thermodynamic quantity which establishes the behavior of any chemical or biological system at or near equilibrium. For example, this quantity governs ligand binding-unbinding processes, diffusion of small molecules across cell membranes, conformational transitions of biomolecules and many more. Therefore, the knowledge of the associated free energy landscape is crucial for the comprehensive description of any biophysical process. However, determining a reliable free energy map is often a difficult task to perform. Non-equilibrium simulations could serve as a powerful tool for characterizing equilibrium properties of biomolecular systems, including equilibrium free energy differences. Here, we present an application of non-equilibrium constant velocity steered molecular dynamics (cv-SMD) simulations in conjunction with Jarzynski equality to probe the binding-unbinding process of ligands from viral RNA elements. Following this approach, we characterized these processes using equilibrium free energy profile and identified conformational transitions associated with them.