Functionally relevant conformational dynamics of water-soluble proteins

• Published in: Molecular biology (New York) 2013, Vol.47 (1), p.149-160
• Main Authors: Novikov, G. V., Sivozhelezov, V. S., Shaitan, K. V.
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Crystal structure; Crystallography; Human Genetics; Life Sciences; Molecular biology; Proteins; Structural and Functional Analysis of Biopolymers and Their Complexes
• ISSN: 0026-8933; 1608-3245
• DOI: 10.1134/S0026893313010111

A study of the functional-relevant dynamics of three typical water-soluble proteins, including Calmodulin, Src-tyrosine kinase, and a repressor of the trip operon, has been reported. The application of state-of-art methods of structural bioinformatics allowed us to identify the dynamics seen in the X-ray structures of the investigated proteins associated with their specific biological functions. In addition, technique of normal mode analysis reveals the most probable directions of the functionally relevant motions for all proteins. Importantly, the overall type of the motions observed in the lowest-frequency modes was very similar to the motions seen from the analysis of the X-ray data of the examined macromolecules. Thus, it was shown that the large-scale, as well as local, conformational motions of the proteins might already be predetermined at the level of their tertiary structures. In particular, the determining factor might be the specific fold of the α-helices. Thus, the functionally relevant in vivo dynamics of the investigated proteins might be evolutionarily formed by natural selection at the level of the spatial topology.