Why are the low-energy protein normal modes evolutionarily conserved?

Abstract

Proteins fluctuate, and such fluctuations are functionally important. As with any functionally relevant trait, it is interesting to study how fluctuations change during evolution. In contrast with sequence and structure, the study of the evolution of protein motions is much more recent. Yet, it has been shown that the overall fluctuation pattern is evolutionarily conserved. Moreover, the lowest-energy normal modes have been found to be the most conserved. The reasons behind such a differential conservation have not been explicitly studied. There are two limiting explanations. A "biological"explanation is that because such modes are functional, there is natural selection pressure against their variation. An alternative "physical" explanation is that the lowest-energy normal modes may be more conserved because they are just more robust with respect to random mutations. To investigate this issue, I studied a set of globin-like proteins using a perturbed elastic network model (ENM) of the effect of random mutations on normal modes. I show that the conservation predicted by the model is in excellent agreement with observations. These results support the physical explanation: the lowest normal modes are more conserved because they are more robust.