The effective degeneracy of protein normal modes

摘要

Normal modes are frequently computed and used to portray protein dynamics and interpret protein conformational changes. In this work, we investigate the nature of normal modes and find that the normal modes of proteins, especially those at the low frequency range (0- 600 cm(-1)), are highly susceptible to degeneracy. Two or more modes are degenerate if they have the same frequency and consequently any orthogonal transformation of them also is a valid representation of the mode subspace. Thus, degenerate modes can no longer characterize unique directions of motions as regular modes do. Though the normal modes of proteins are usually of different frequencies, the difference in frequency between neighboring modes is so small that, under even slight structural uncertainty that unavoidably exists in structure determination, it can easily vanish and as a result, a mode becomes effectively degenerate with its neighboring modes. This can be easily observed in that some modes seem to disappear and their matching modes cannot be found when the structure used to compute the modes is modified only slightly. Weterm this degeneracy the effective degeneracy of normal modes. This work is built upon our recent discovery that the vibrational spectrum of globular proteins is universal. The high density of modes observed in the vibrational frequency spectra of proteins renders their normal modes highly susceptible to degeneracy, under even the smallest structural uncertainty. Indeed, we find the degree of degeneracy of modes is proportional to the density of modes in the vibrational spectrum. This means that for modes at the same frequency, degeneracy is more severe for larger proteins. Degeneracy exists also in the modes of coarse-grained models, but to a much lesser extent than those of all-atom models. In closing, we discuss the implications of the effective degeneracy of normal modes: how it may significantly affect the ways in which normal modes are used in various normal modes-based applications.