Approximate normal mode analysis based on vibrational subsystem analysis with high accuracy and efficiency.

Normal mode analysis (NMA) has been proven valuable in modeling slow conformational dynamics of biomolecular structures beyond the reach of direct molecular simulations. However, it remains computationally expensive to directly solve normal modes for large biomolecular systems. In this study, we have evaluated the accuracy and efficiency of two approximate NMA protocols-one based on our recently proposed vibrational subsystem analysis (VSA), the other based on the rotation translation block (RTB), in comparison with standard NMA that directly solves a full Hessian matrix. By properly accounting for flexibility within blocks of residues or atoms based on a subsystem-environment partition, VSA-based NMA has attained a much higher accuracy than RTB and much lower computing cost than standard NMA. Therefore, VSA enables accurate and efficient calculations of normal modes from all-atom or coarse-grained potential functions, which promise to improve conformational sampling driven by low-frequency normal modes.