Ab Initio MD Simulations of the Bronsted Acidity of Glutathione in Aqueous Solutions: Predicting pK(a) Shifts of the Cysteine Residue

Tummanapelli, Anil Kumar and Vasudevan, Sukumaran (2016) Ab Initio MD Simulations of the Bronsted Acidity of Glutathione in Aqueous Solutions: Predicting pK(a) Shifts of the Cysteine Residue. In: JOURNAL OF PHYSICAL CHEMISTRY B, 119 (49). pp. 15353-15358.

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Abstract

The tripeptide glutathione (GSH) is one of the most abundant peptides and the major repository for nonprotein sulfur in both animal and plant cells. It plays a critical role in intracellular oxidative stress management by the reversible formation of glutathione disulfide with the thiol-disulfide pair acting as a redox buffer. The state of charge of the ionizable groups of GSH can influence the redox couple, and hence the pK(a) value of the cysteine residue of GSH is critical to its functioning. Here we report ab initio Car-Parrinello molecular dynamics simulations of glutathione solvated by 200 water molecules, all of which are considered in the simulation. We show that the free-energy landscape for the protonation-deprotonation reaction of the cysteine residue of GSH computed using metadynamics sampling provides shift in the dissociation constant values as compared with the isolated accurate estimates of the pK(a) and correctly predicts the cysteine amino acid.

Item Type:	Journal Article
Publication:	JOURNAL OF PHYSICAL CHEMISTRY B
Publisher:	AMER CHEMICAL SOC
Additional Information:	Copy right for this article belongs to the AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Department/Centre:	Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	07 Jan 2016 06:11
Last Modified:	07 Jan 2016 06:11
URI:	http://eprints.iisc.ac.in/id/eprint/53037

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