Abstract
Coarse-grained simulations have emerged as invaluable tools for studying conformational changes in biomolecules. To evaluate the effectiveness of computationally inexpensive coarse-grained models in studying global and local dynamics of large protein systems like aminoacyl-tRNA synthetases, we have performed coarse-grained normal mode analysis, as well as principle component analysis on trajectories of all-atom and coarse-grained molecular dynamics simulations for three aminoacyl-tRNA synthetases—Escherichia coli methionyl-tRNA synthetase, Thermus thermophilus leucyl-tRNA synthetase, and Enterococcus faecium prolyl-tRNA synthetase. In the present study, comparison of predicted dynamics based on B-factor and overlap calculations revealed that coarse-grained methods are comparable to the all-atom simulations in depicting the intrinsic global dynamics of the three enzymes. However, the principal component analyses of the motions obtained from the all-atom molecular dynamics simulations provide a superior description of the local fluctuations of these enzymes. In particular, the all-atom model was able to capture the functionally relevant substrate-induced dynamical changes in prolyl-tRNA synthetase. The alteration in the coupled dynamics between the catalytically important proline-binding loop and its neighboring structural elements due to substrate binding has been characterized and reported for the first time. Taken together, the study portrays comparable and contrasting situations in studying the functional dynamics of large multi-domain aminoacyl-tRNA synthetases using coarse-grained and all-atom simulation methods. FigureSubstrate-induced conformational change in E. facium prolyl-tRNA synthetase Electronic supplementary materialThe online version of this article (doi:10.1007/s00894-014-2245-1) contains supplementary material, which is available to authorized users.
Highlights
Aminoacyl-tRNA synthetases (AARSs) play a pivotal role in cellular protein synthesis and viability [1]
AARSs are responsible for accurately attaching an amino acid onto the corresponding tRNA molecule in a two-step reaction
The activated amino acid is transferred to the 3′-end of its corresponding tRNA molecule to be used for protein synthesis
Summary
Aminoacyl-tRNA synthetases (AARSs) play a pivotal role in cellular protein synthesis and viability [1]. The activated amino acid is transferred to the 3′-end of its corresponding tRNA molecule to be used for protein synthesis. The central aminoacylation domain is responsible for the selection and activation of the correct amino acid. The anticodon binding domain is often responsible for selecting the corresponding tRNA molecule. In the course of evolution, additional domains were either appended or inserted to the two-domain structure to enhance catalytic efficiency and confer tRNA selection [1]. In some cases, these appended domains exclusively catalyze editing reactions by hydrolyzing the misactivated amino acids (pretransfer editing reaction) and/or misaminoacylated tRNA (post-transfer editing reaction) [2]
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