Choline Chloride as a Nano‐Crowder Protects HP‐36 from Urea‐Induced Denaturation: Insights from Solvent Dynamics and Protein‐Solvent Interactions. Issue 6 (7th February 2020)

• Record Type: Journal Article
• Authors: Maity, Atanu; Sarkar, Soham; Theeyancheri, Ligesh; Chakrabarti, Rajarshi
• Is Part Of: Chemphyschem. Volume 21:Issue 6(2020)
• Page Start: 552
• Page End: 567
• Publication Date: 2020-02-07
• Subjects: cosolvent dynamics -- hydrogen bond dynamics -- molecular dynamics simulation -- Nano-crowder -- subdiffusion; Chemistry, Physical and theoretical -- Periodicals; 541.05
• DOI: 10.1002/cphc.201901078
• Languages: English
• ISSNs: 1439-4235

Abstract

Abstract: Urea at sufficiently high concentration unfolds the secondary structure of proteins leading to denaturation. In contrast, choline chloride (ChCl) and urea, in 1 : 2 molar ratio, form a deep eutectic mixture, a liquid at room temperature, protecting proteins from denaturation. In order to get a microscopic picture of this phenomenon, we perform extensive all‐atom molecular dynamics simulations on a model protein, HP‐36. Based on our calculation of Kirkwood‐Buff integrals, we analyze the relative accumulation of urea and ChCl around the protein. Additional insights are drawn from the translational and rotational dynamics of solvent molecules and hydrogen bond auto‐correlation functions. In the presence of urea, water shows slow subdiffusive dynamics around the protein owing to a strong interaction of water with the backbone atoms. Urea also shows subdiffusive motion. The addition of ChCl further slows down the dynamics of urea, restricting its accumulation around the protein backbone. Adding to this, choline cations in the first solvation shell of the protein show the strongest subdiffusive behavior. In other words, ChCl acts as a nano‐crowder by excluding urea from the protein backbone and thereby slowing down the dynamics of water around the protein. This prevents the protein from denaturation and makes it structurally rigid, which is supported by the smaller radius of gyration and root mean square deviation values of HP‐36. Abstract : Inhibiting denaturation : Choline chloride in a 1 : 2 ratio with urea prevents denaturation of the model protein HP‐36. The presence of choline chloride makes the surroundings of the protein largely crowded, thus slowing down the translational and rotational motions of the solvent and co‐solvent molecules, and also the dynamics of the hydrogen bonds between protein and surrounding moieties. This resuls in the restriction of the conformational flexibility of the protein.