Book of Abstracts: Albany 2009

category image Albany 2009
Conversation 16
June 16-20 2009
© Adenine Press (2008)

Allostery in tRNA Synthetases elucidated from MD simulations and Protein Structure Networks

tRNA synthetases (aaRS) are enzymes crucial in the translation of genetic code. The enzyme accylates the acceptor stem of tRNA by the congnate amino acid bound at the active site, when the anti-codon is recognized by the anti-codon site of aaRS. In a typical aaRS, the distance between the anti-codon region and the amino accylation site is approximately 70 Å. We have investigated this allosteric phenomenon at molecular level by MD simulations followed by the analysis of protein structure networks (PSN) of non-covalent interactions. Specifically, we have generated conformational ensembles by performing MD simulations on different liganded states of methionyl tRNA synthetase (MetRS) from Escherichia coli and tryptophenyl tRNA synthetase (TrpRS) from Human. The correlated residues during the MD simulations are identified by cross correlation maps. We have identified the amino acids connecting the correlated residues by the shortest path between the two selected members of the PSN. The frequencies of paths have been evaluated from the MD snapshots[1]. The conformational populations in different liganded states of the protein have been beautifully captured in terms of network parameters such as hubs, cliques and communities[2]. These parameters have been associated with the rigidity and plasticity of the protein conformations and can be associated with free energy landscape. A comparison of allosteric communication in MetRS and TrpRS [3] elucidated in this study highlights diverse means adopted by different enzymes to perform a similar function. The computational method described for these two enzymes can be applied to the investigation of allostery in other systems.

References and Footnotes
  1. Amit Ghosh and Saraswathi Vishveshwara, Communication pathways from the anti-codon region to the aminoacylation site in Methionyl tRNA Synthetase: Molecular dynamics simulations and the structure network analysis, PNAS 104: 15711-15716 (2007)
  2. Amit Ghosh and Saraswathi Vishveshwara, Variations in clique and community patterns in protein structures during allosteric communication: Investigation of dynamically equilibrated structures of methionyl tRNA synthetase complexes, Biochemistry 47(44):11398-11407 (2008)
  3. Priti Hansia, Amit Ghosh and Saraswathi Vishveshwara, Ligand dependent Intra and Inter subunit Communication in Human Tryptophanyl tRNA Synthetase as Deduced from the Dynamics of Structure Networks (submitted for publication) (2009).

Amit Ghosh1a
Priti Hansia1
Saraswathi Vishveshwara 1*

1 Molecular Biophysics Unit
Indian Institute of Science
Bangalore, 560012, India
aCurrent address: Institute for Genomic Biology
UIUC,Urbana, IL

Phone: +91-80-22832611
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