分子动力学模拟尿素对水溶液中蛋白质构象转变的影响

The effect of urea on the conformational transition of protein in aqueous by molecular dynamics simulations

采用分子动力学方法和全原子模型研究尿素和水分子对模型蛋白S-肽链结构转化的影响。模拟结果显示S-肽链的变性速率常数k值随着尿素浓度的增加而先降低后升高,在尿素浓度为2.9 mol/L时达到最低值。模拟了不同尿素浓度下尿素-肽链、水-肽链以及肽链分子氢键的形成状况。结果表明:尿素浓度较低时,尿素分子与S-肽链的极性氨基酸侧链形成氢键,但不破坏其分子内的骨架氢键,尿素在S-肽链水化层外形成限制性空间,增强了S-肽链的稳定性。随着尿素的升高,尿素分子进入S-肽链内部并与其内部氨基酸残基形成氢键,导致S-肽链的骨架氢键丧失,S-肽链发生去折叠。上述模拟结果与文献报道的实验结果一致,从分子水平上揭示了尿素对蛋白质分子结构变化的影响机制,对于研究和发展蛋白质折叠及稳定化技术具有指导意义。

The effect of urea and water molecular to the S-peptide conformational transition in the protein sample was studied with all atom model by molecular dynamics method. The simulation showed that with the increase of urea concentration led to, firstly, a reduction and then an increase of the unfolding rate constant. The minimum unfolding rate constant was reached when the urea concentration was 2.9 mol/L. The hydrogen bond between S-peptide and urea, S-peptide and water, and within S-peptide were studied. The results showed that at a low concentration of urea, the hydrogen bonds between urea and the side chains of polar amino acid residues generated a urea confinement around the surface of S-peptide, giving an enhanced stability to S- peptide. At a high concentration of urea, however, the intra-molecular hydrogen bonds in the native S-peptide were overtaken by the hydrogen bonds between urea and amino acid residues located at backbone of peptide, leading to the unfolding of S-peptide. The results were similar to that reported elsewhere. The mechanism of urea to the protein conformational transition revealed in molecnlar level was useful in development protein stabilization and protein refolding technic.