Atomic-scale mechanism of met repressor function

COMP 211

Jieru Zheng, jz7@duke.edu, Ilya Balabin, and David N. Beratan, beratan@chem.duke.edu. Department of Chemistry, Duke university, Box 90348, Durham, NC 27708
The met repressor is a transcription regulator of structural genes in the methionine biosynthetic pathway. A product of the pathway, S-adenosylmethionine (SAM), is known to facilitate binding of the repressor to the operator (met box), acting as a corepressor. Experiments show no evidence of allosteric effects in SAM binding, suggesting that its function may involve electrostatic interactions with DNA. We explore the SAM corepressor function using molecular dynamics (MD) simulations and essential dynamics analysis. Three systems based on the protein-DNA complex were modeled and simulated: the complex with SAM, the complex without SAM, and the complex with SAH (SAM analog with much weaker electrostatic interactions). Each system was solvated in TIP3 water, and Na+ and Cl- counterions were added. Following that, each system was equilibrated for about 6ns using the CHARMM force field. Essential dynamics-based analysis of the MD trajectories reveals atomic scale details of the protein-DNA and protein-protein interactions, elaborating the corepressor function in the gene transcription mechanism.