fSUB: normal mode analysis with flexible substructures.

In this paper, we report a novel normal-mode analysis for supramolecular complexes, named fSUB. The method models a complex as a group of flexible substructures. The low-frequency substructure modes are first determined with substructures in isolation, and the motions of the whole complex are then calculated on the basis of substructure modes and substructure-substructure interactions. The calculation of modes in fSUB requires modal analysis without initial energy minimization, which is essential for maintaining energetic and structural consistency between substructures and whole complex. Compared with other coarse-grained methods, such as the RTB method, fSUB delivers much more accurate modes for the complex and allows for the choice of much larger substructures. The method can also accommodate any type of substructure arrangement including covalent bonds across the interface. In tests on molecular chaperonin GroEL (7350 residues) and HK97 capsid complex (118,092 residues), fSUB was shown to be much more efficient in terms of combined accuracy and demand of computing resources. Our results clearly demonstrated the vital importance of including substructure flexibility in complex modal analysis, as the deformational patterns of substructures were found to play an important role even in the lowest frequency modes of the whole complex.