TITLE An NMA - Guided Path Planning

This paper presents a new method for computing macromolecular motions based on the combination of path planning algorithms, originating from robotics research, and elastic network normal mode analysis. The low-frequency normal modes are regarded as the collective degrees of freedom of the molecule. Geometric path planning algorithms are used to explore these collective degrees of freedom in order to find possible large-amplitude conformational changes. To overcome the limits of the harmonic approximation, which is valid in the vicinity of the minimum energy structure, and to get larger conformational changes, normal mode calculations are iterated during the exploration. Initial results show the efficiency of the proposed method to compute large-amplitude conformational transitions in proteins, requiring few normal mode calculations. We present the computed transition between the open and closed structures of adenylate kinase. This transition, important for its biological function, involves large-amplitude domain motions. The obtained motion correlates well with results presented in related works.