Shukla Diwakar, Shinde Chetan, Trout Bernhardt L
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
J Phys Chem B. 2009 Sep 17;113(37):12546-54. doi: 10.1021/jp810949t.
Estimation of the thermodynamic properties of proteins in mixed solvents is crucial for understanding the effect of cosolvents on rates and equilibrium constants of reactions involving proteins. In this paper, a predictive, molecular level approach for the study of preferential interactions of proteins with either water or cosolvents based on all-atom, statistical mechanical models is used to calculate the preferential interaction coefficient of proteins. Model systems comprised of the cosolvents urea, glycerol, arginine hydrochloride, guanidinium hydrochloride, and glucose with the proteins RNase T1, Hen egg white lysozyme, and alpha-chymotrypsinogen A(alpha-Cgn A) are studied. Trajectories in the range 10-20 ns are analyzed in order to validate this method. From the computational perspective, several key aspects of these simulations are investigated in detail. Protein dynamics and cosolvent dynamics play an important role in the estimation of preferential interaction coefficients, and in determining the length of simulation required to get a reliable estimate of the coefficient. Further, simulation results are found to be sensitive to changes in the cosolvent force field parameters. A comparison of simulated and experimental data is performed for two different force field parameters for glycerol and urea in order to assess the sensitivity of the preferential interaction coefficient to changes in force field parameters. This work highlights the effect of length of simulation, cosolvent force field parameters, and protein structure fluctuations on estimation of the preferential interaction coefficient of proteins in mixed solvents.
估算蛋白质在混合溶剂中的热力学性质对于理解共溶剂对涉及蛋白质的反应速率和平衡常数的影响至关重要。在本文中，基于全原子统计力学模型，采用一种预测性的分子水平方法来研究蛋白质与水或共溶剂之间的优先相互作用，以计算蛋白质的优先相互作用系数。研究了由共溶剂尿素、甘油、盐酸精氨酸、盐酸胍和葡萄糖与蛋白质核糖核酸酶T1、鸡蛋清溶菌酶和α-胰凝乳蛋白酶原A（α-Cgn A）组成的模型体系。分析了10 - 20纳秒范围内的轨迹以验证该方法。从计算角度详细研究了这些模拟的几个关键方面。蛋白质动力学和共溶剂动力学在优先相互作用系数的估算以及确定获得可靠系数估算所需的模拟长度方面起着重要作用。此外，发现模拟结果对共溶剂力场参数的变化敏感。为了评估优先相互作用系数对力场参数变化的敏感性，针对甘油和尿素的两种不同力场参数进行了模拟数据与实验数据的比较。这项工作突出了模拟长度、共溶剂力场参数和蛋白质结构波动对估算混合溶剂中蛋白质优先相互作用系数的影响。
