No abstract

Internal protein dynamics is essential for biological function. During evolution, protein divergence is functionally constrained: properties more relevant for function vary more slowly than less important properties. Thus, if protein dynamics is relevant for function, it should be evolutionary conserved. In contrast with the well-studied evolution of protein structure, the evolutionary divergence of protein dynamics has not been addressed systematically before, apart from a few case studies. X-Ray diffraction analysis gives information not only on protein structure but also on B-factors, which characterize the flexibility that results from protein dynamics. Here we study the evolutionary divergence of protein backbone dynamics by comparing the C(alpha) flexibility (B-factor) profiles for a large dataset of homologous proteins classified into families and superfamilies. We show that C(alpha) flexibility profiles diverge slowly, so that they are conserved at family and superfamily levels, even for pairs of proteins with nonsignificant sequence similarity. We also analyze and discuss the correlations among the divergences of flexibility, sequence, and structure.

We present a procedure to explore the global dynamics shared between members of the same protein family. The method allows the comparison of patterns of vibrational motion obtained by Gaussian network model analysis. After the identification of collective coordinates that were conserved during evolution, we quantify the common dynamics within a family. Representative vectors that describe these dynamics are defined using a singular value decomposition approach. As a test case, the globin heme-binding family is considered. The two lowest normal modes are shown to be conserved within this family. Our results encourage the development of models for protein evolution that take into account the conservation of dynamical features.