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Solvent Sensitivity of Protein Unfolding: Dynamical Study of Chicken Villin Headpiece Subdomain in Water Ethanol Binary Mixture

Ghosh, Rikhia and Roy, Susmita and Bagchi, Biman (2013) Solvent Sensitivity of Protein Unfolding: Dynamical Study of Chicken Villin Headpiece Subdomain in Water Ethanol Binary Mixture. In: JOURNAL OF PHYSICAL CHEMISTRY B, 117 (49, SI). pp. 15625-15638.

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Official URL: http://dx.doi.org/10.1021/jp406255z


We carry out a series of long atomistic molecular dynamics simulations to study the unfolding of a small protein, chicken villin headpiece (HP-36), in water-ethanol (EtOH) binary mixture. The prime objective of this work is to explore the sensitivity of protein unfolding dynamics toward increasing concentration of the cosolvent and unravel essential features of intermediates formed in search of a dynamical pathway toward unfolding. In water ethanol binary mixtures, HP-36 is found to unfold partially, under ambient conditions, that otherwise requires temperature as high as similar to 600 K to denature in pure aqueous solvent. However, an interesting course of pathway is observed to be followed in the process, guided by the formation of unique intermediates. The first step of unfolding is essentially the separation of the cluster formed by three hydrophobic (phenylalanine) residues, namely, Phe-7, Phe-11, and Phe-18, which constitute the hydrophobic core, thereby initiating melting of helix-2 of the protein. The initial steps are similar to temperature-induced unfolding as well as chemical unfolding using DMSO as cosolvent. Subsequent unfolding steps follow a unique path. As water-ethanol shows composition-dependent anomalies, so do the details of unfolding dynamics. With an increase in cosolvent concentration, different partially unfolded intermediates are found to be formed. This is reflected in a remarkable nonmonotonic composition dependence of several order parameters, including fraction of native contacts and protein-solvent interaction energy. The emergence of such partially unfolded states can be attributed to the preferential solvation of the hydrophobic residues by the ethyl groups of ethanol. We further quantify the local dynamics of unfolding by using a Marcus-type theory.

Item Type: Journal Article
Additional Information: copyright for this article belongs to AMER CHEMICAL SOC,USA
Department/Centre: Division of Chemical Sciences > Solid State & Structural Chemistry Unit
Date Deposited: 22 Jan 2014 04:35
Last Modified: 22 Jan 2014 04:35
URI: http://eprints.iisc.ac.in/id/eprint/48209

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