Methyl Dynamics in Biological Macromolecules: Evolution and Implications

Abstract

Recent studies have discovered strong differences between the dynamics of proteins and nucleic acids (RNA and DNA). This is especially clear at low hydration and low temperatures where the dynamics of methyl groups is emphasized. Methyl groups are abundant in proteins, but are absent or very rare in RNA and DNA. We present a hypothesis regarding the role of methyl groups as intrinsic plasticizers in proteins and how this can be seen as a result of evolutionary selection to facilitate protein dynamics, and therefore, activity. In support of this hypothesis we demonstrate the profound effect methyl groups have on protein dynamics and note the apparent correlation of methyl group content in different proteins classes and the role of molecular flexibility for those classes. Moreover, we have observed form literature data and simulation that the fastest methyl groups of some enzymes appear around dynamical centers such as hinges or active sites. Methyl groups are also of tremendous importance from a hydrophobicity/folding/entropy perspective. These significant roles, however, should not preclude the recognition of a role for methyl groups in the dynamics of biomolecules.