title: Composition dependent multiple structural transformations of myoglobin in aqueous ethanol solution: a combined experimental and theoretical study.
abstract: Experimental studies (circular dichroism and ultra-violet (UV) absorption spectra) and large scale atomistic molecular dynamics simulations (accompanied by order parameter analyses) are combined to establish a number of remarkable (and unforeseen) structural transformations of protein myoglobin in aqueous ethanol mixture at various ethanol concentrations. The following results are particularly striking. (1) Two well-defined structural regimes, one at xEtOH ∼ 0.05 and the other at xEtOH ∼ 0.25, characterized by formation of distinct partially folded conformations and separated by a unique partially unfolded intermediate state at xEtOH ∼ 0.15, are identified. (2) Existence of non-monotonic composition dependence of (i) radius of gyration, (ii) long range contact order, (iii) residue specific solvent accessible surface area of tryptophan, and (iv) circular dichroism spectra and UV-absorption peaks are observed. Interestingly at xEtOH ∼ 0.15, time averaged value of the contact order parameter of the protein reaches a minimum, implying that this conformational state can be identified as a molten globule state. Multiple structural transformations well known in water-ethanol binary mixture appear to have considerably stronger effects on conformation and dynamics of the protein. We compare the present results with studies in water-dimethyl sulfoxide mixture where also distinct structural transformations are observed along with variation of co-solvent composition.
authors.affiliation: Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012, India.
authors.forename: R
authors.initials: R
authors.lastname: Ghosh
authors.affiliation: Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012, India.
authors.forename: R N
authors.initials: RN
authors.lastname: Samajdar
authors.affiliation: Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Aninda Jiban
authors.initials: AJ
authors.lastname: Bhattacharyya
authors.affiliation: Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012, India.
authors.forename: B
authors.initials: B
authors.lastname: Bagchi
mesh_terms: D000818:Animals; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D000431:Ethanol / Q000737:chemistry*; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D009211:Myoglobin / Q000737:chemistry*; D055550:Protein Stability; D017433:Protein Structure, Secondary; D012399:Rotation; D012996:Solutions; D014867:Water / Q000737:chemistry*
chemical_list: D009211:Myoglobin; D012996:Solutions; D014867:Water; D000431:Ethanol; D004121:Dimethyl Sulfoxide