Gupta Shubhangi, Sasidhar Yellamraju U
Department of Chemistry, Indian Institute of Technology Bombay , Powai, Mumbai 400 076, India.
J Phys Chem B. 2017 Feb 16;121(6):1268-1283. doi: 10.1021/acs.jpcb.6b12219. Epub 2017 Feb 3.
The rate-limiting step for the folding of the helix-turn-helix (HTH) protein, Z34C, involves β-turn region DPNL. This reverse turn has been observed to be part of the transition state in the folding process for Z34C, influencing its folding rates. Molecular dynamics simulations were performed on this turn peptide and its two mutants, D20A and P21A, to study turn formation using GROMOS54A7 force field. We find that this region has a turn propensity of its own, and the highest turn propensity is observed for the wild-type, which correlates well with available experimental results. We also find that a slight unfavorable change in ΔG causes a drastic change in the folding rates of HTH motif and a mechanistic interpretation is given. Implications of these observations for the folding of the HTH protein Z34C are discussed.
螺旋-转角-螺旋（HTH）蛋白Z34C折叠的限速步骤涉及β-转角区域DPNL。已观察到这种反向转角是Z34C折叠过程中过渡态的一部分，影响其折叠速率。使用GROMOS54A7力场对该转角肽及其两个突变体D20A和P21A进行了分子动力学模拟，以研究转角的形成。我们发现该区域本身具有形成转角的倾向，野生型的转角倾向最高，这与现有的实验结果相关性良好。我们还发现ΔG的轻微不利变化会导致HTH基序折叠速率的急剧变化，并给出了机理解释。讨论了这些观察结果对HTH蛋白Z34C折叠的影响。
