title: Can an ammonium-based room temperature ionic liquid counteract the urea-induced denaturation of a small peptide?
abstract: The folding/unfolding equilibrium of proteins in aqueous medium can be altered by adding small organic molecules generally termed as co-solvents. Denaturants such as urea are instrumental in the unfolding of proteins while protecting osmolytes favour the folded ensemble. Recently, room temperature ionic liquids (ILs) have been shown to counteract the deleterious effect of urea on proteins. In this paper, using atomistic molecular dynamics we show that a ternary mixture containing a particular ammonium-based IL, triethylammonium acetate (TEAA), and urea (in 1 : 5 molar ratio) helps a small 15-residue S-peptide analogue regain most of its native structure, whereas a binary aqueous mixture containing a large amount of urea alone completely distorts it. Our simulations show that the denaturant urea directly interacts with the peptide backbone in the binary mixture while for the ternary mixture both urea as well as the IL are preferentially excluded from the peptide surface.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai - 400076, India. rajarshi@chem.iitb.ac.in.
authors.forename: Soumadwip
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai - 400076, India. rajarshi@chem.iitb.ac.in.
authors.forename: Souvik
authors.identifier: http://orcid.org/0000-0002-4366-5681
authors.initials: S
authors.lastname: Dey
authors.affiliation: Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai - 400076, India. rajarshi@chem.iitb.ac.in.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Patel
authors.affiliation: Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai - 400076, India. rajarshi@chem.iitb.ac.in.
authors.forename: Rajarshi
authors.identifier: http://orcid.org/0000-0002-9279-7066
authors.initials: R
authors.lastname: Chakrabarti
mesh_terms: D000595:Amino Acid Sequence; D064751:Ammonium Compounds / Q000737:chemistry*; D052578:Ionic Liquids / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry; D013696:Temperature; D014508:Urea / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D064751:Ammonium Compounds; D052578:Ionic Liquids; D010455:Peptides; D012997:Solvents; D014867:Water; D014508:Urea