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.
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Funding
JDN and APS acknowledge DOE support through the EPSCoR program (grant DE-FG02–08ER46528) and support from SNS through UT-Battelle. HON acknowledges support of the Center for Structural Molecular Biology (CSMB) funded by the Office of Biological and Environmental Research under FWP ERKP291, using facilities supported by the U.S. Department of Energy. Oak Ridge National Laboratory is managed by UT-Battelle, LLC for the U.S. Department of Energy under contract No. DE-AC05–00OR22725.
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Nickels, J.D., Curtis, J.E., O’Neill, H. et al. Role of methyl groups in dynamics and evolution of biomolecules. J Biol Phys 38, 497–505 (2012). https://doi.org/10.1007/s10867-012-9268-6
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DOI: https://doi.org/10.1007/s10867-012-9268-6