Borgohain Gargi, Paul Sandip
Department of Chemistry, Indian Institute of Technology , Guwahati 781039, India.
J Phys Chem B. 2016 Mar 10;120(9):2352-61. doi: 10.1021/acs.jpcb.5b10968. Epub 2016 Feb 24.
Classical molecular dynamics simulation of GB1 peptide (a 16-residue β-hairpin) in different osmotic environments is studied. Urea is used for denaturation of the peptide, and trimethylamine-N-oxide (TMAO) is used to offset the effect of urea. Protein-urea electrostatic interactions are found to play a major role in protein-denaturation. To emphasize on protein protecting action of TMAO against urea, two different models of TMAO are used, viz., the Kast model and the Osmotic model. We observe that the Osmotic model of TMAO gives the best protection to counteract urea's action when used in ratio 1:2 of urea:TMAO (i.e., reverse ratio). This is because the presence of TMAO makes urea-protein electrostatic interactions more unfavorable. Preferential solvation of TMAO molecules by urea (and water) molecules is also observed, which causes depletion in the number of urea molecules in the vicinity of the protein. The calculations of intraprotein hydrogen bonds between different residues of protein further reveal the breaking of backbone hydrogen bonds of residues 2 and 15 in the presence of urea, and the same is preserved in the presence of TMAO. Free energy landscapes show that the narrowest distribution is obtained for the osmotic TMAO model when used in reverse ratio.
研究了GB1肽（一种16个残基的β-发夹结构）在不同渗透环境下的经典分子动力学模拟。使用尿素使肽变性，并使用三甲胺-N-氧化物（TMAO）来抵消尿素的作用。发现蛋白质-尿素静电相互作用在蛋白质变性中起主要作用。为了强调TMAO对尿素的蛋白质保护作用，使用了两种不同的TMAO模型，即Kast模型和渗透模型。我们观察到，当以尿素：TMAO的1:2比例（即相反比例）使用时，TMAO的渗透模型对抵消尿素的作用提供了最佳保护。这是因为TMAO的存在使尿素-蛋白质静电相互作用更不利。还观察到尿素（和水）分子对TMAO分子的优先溶剂化作用，这导致蛋白质附近尿素分子数量减少。蛋白质不同残基之间的蛋白质内氢键计算进一步揭示了在尿素存在下残基2和15的主链氢键断裂，而在TMAO存在下则得以保留。自由能景观表明，当以相反比例使用时，渗透TMAO模型获得的分布最窄。
