In this study, a normal mode analysis, named phase integrated method (PIM), is developed for computing modes of biomolecules in a crystalline environment. PIM can calculate low-frequency modes on one or a few asymmetric units (AUs) and generate exact modes of a whole unit cell according to space group symmetry, while the translational symmetry between unit cells is maintained via the periodic boundary condition. Therefore, the method can dramatically reduce computational cost in mode calculation in the presence of crystal symmetry. PIM also has an option to map modes onto a single AU to form an orthonormalized mode set, which can be directly applied to normal-mode-based thermal parameter refinement in X-ray crystallography. The performance of PIM was tested on all 65 space groups available in protein crystals (one protein for each space group) and on another set of 83 ultra-high-resolution X-ray structures. The results showed that considering space group symmetry in mode calculation is crucial for accurately describing vibrational motion in a crystalline environment. Moreover, the optimal inter-AU packing stiffness was found to be about 60% of that of intra-AU interactions (non-bonded interaction only).
Published by Elsevier Ltd.