Role of methyl groups in dynamics and evolution of biomolecules

Abstract

Recent studies have discovered strong differences between the dynamics of nucleic acids (RNA and DNA) and proteins, especially at low hydration and low temperatures. This difference is caused primarily by dynamics of methyl groups that are abundant in proteins, but are absent or very rare in RNA and DNA. In this paper, we present a hypothesis regarding the role of methyl groups as intrinsic plasticizers in proteins and their evolutionary selection to facilitate protein dynamics and activity. We demonstrate the profound effect methyl groups have on protein dynamics relative to nucleic acid dynamics, and note the apparent correlation of methyl group content in protein classes and their need for molecular flexibility. Moreover, we note 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, complement our hypothesis rather than preclude the recognition of methyl groups in the dynamics and evolution of biomolecules.Electronic supplementary material The online version of this article (doi:10.1007/s10867-012-9268-6) contains supplementary material, which is available to authorized users.

Structural effects of modified ribonucleotides and magnesium in transfer RNAs

“…The accumulation of methylations lowers the biomolecular rigidity and activation energy in aqueous phase, thus methylation has been hypothesized to be a promoter of an evolutionary path where the information storage and catalytic functions of RNA eventually are transferred to methyl-abundant DNAs and proteins, respectively. [70] Specifically a large number of experiments have studied the activities of methylation enzymes of tRNA,[71,72,73,74] as well as the methylation influence on tRNA function. [52,75] However it is difficult to attribute structural changes to methylation directly using current models, because some effects of methylation are not straightforward.…”

Protein dynamics: from rattling in a cage to structural relaxation

“…2B), and its suppression was shown to be important for effective long-term biopreservation. 18,19,42,84,94,95,102,148 We speculate that the absence (or very low number) of methyl View Article Online groups in nucleic acids (RNA and DNA) might be one of the reasons for much stronger slowing down of their dynamics with a decrease in temperature (Fig. 8).…”

“…These relaxations usually have a broad distribution of relaxation times with Arrhenius-like temperature dependence. 18,19,39,42,84,[92][93][94][95] These observations suggest that methyl groups might play the role of internal plasticizers by facilitating protein dynamics even under extreme conditions of low hydration or temperature. 18,19,39,42,84,[92][93][94][95] All proteins contain a significant number of methyl groups.…”

“…18,19,39,42,84,[92][93][94][95] All proteins contain a significant number of methyl groups. methyl group rotations, phenyl ring flips) exist in proteins.…”

Dynamics and Rigidity in an Intrinsically Disordered Protein, β-Casein

“…Indeed, methyl groups are known to act as internal plasticizing agents in proteins; their rotations remain active even at low temperatures and dry conditions and facilitate the dynamics of proteins due to their low activation energies. 53 Fast picosecond dynamics are suppressed by the presence of hydration water in both proteins at T = 170 K. Frozen water stiffens the systems relative to their dry states. This restriction of the amino-acid residue fluctuations is particularly evident in GFP, probably due to its barrel-like structure.…”