title: An efficient Travelling-salesman based Automated Path Searching method for large biomolecular systems

Lizhe Zhu (TALK)

institution: The Hong Kong University of Science and Technology


Locating the minimum free energy paths (MFEPs) between two conformational states is among the most important tasks of biomolecular simulations. Existing path searching methods typically perform local sampling around the path nodes in a pre-selected collective variable (CV) space to allow a gradual downhill evolution of the path towards the MFEP. Despite the wide application of such strategy, the gradual path evolution and the non-trivial a priori choice of CVs are also limiting its overall efficiency and automation. Here we demonstrate that non-local perpendicular sampling can be pursued to accelerate the search, provided that all path nodes are reordered thereafter via a Travelling-salesman scheme. Moreover, path-collective-variables can be computed on-the-fly and used as a coordinate system, minimizing the necessary prior knowledge about the system. Our alternative approach achieves a 5-8 times speedup over existing methods for two peptide systems in vacuum and solution, and is readily applicable to large biomolecules.