Abramyan Tigran M, Hyde-Volpe David L, Stuart Steven J, Latour Robert A
Department of Bioengineering, Clemson University, 501 Rhodes Engineering Research Center, Clemson, South Carolina 29634.
Department of Chemistry, 369 Hunter Laboratories, Clemson University, Clemson, South Carolina 29634.
Biointerphases. 2017 May 17;12(2):02D409. doi: 10.1116/1.4983274.
The use of standard molecular dynamics simulation methods to predict the interactions of a protein with a material surface have the inherent limitations of lacking the ability to determine the most likely conformations and orientations of the adsorbed protein on the surface and to determine the level of convergence attained by the simulation. In addition, standard mixing rules are typically applied to combine the nonbonded force field parameters of the solution and solid phases the system to represent interfacial behavior without validation. As a means to circumvent these problems, the authors demonstrate the application of an efficient advanced sampling method (TIGER2A) for the simulation of the adsorption of hen egg-white lysozyme on a crystalline (110) high-density polyethylene surface plane. Simulations are conducted to generate a Boltzmann-weighted ensemble of sampled states using force field parameters that were validated to represent interfacial behavior for this system. The resulting ensembles of sampled states were then analyzed using an in-house-developed cluster analysis method to predict the most probable orientations and conformations of the protein on the surface based on the amount of sampling performed, from which free energy differences between the adsorbed states were able to be calculated. In addition, by conducting two independent sets of TIGER2A simulations combined with cluster analyses, the authors demonstrate a method to estimate the degree of convergence achieved for a given amount of sampling. The results from these simulations demonstrate that these methods enable the most probable orientations and conformations of an adsorbed protein to be predicted and that the use of our validated interfacial force field parameter set provides closer agreement to available experimental results compared to using standard CHARMM force field parameterization to represent molecular behavior at the interface.
使用标准分子动力学模拟方法预测蛋白质与材料表面的相互作用存在固有限制，即缺乏确定吸附在表面的蛋白质最可能的构象和取向以及确定模拟达到的收敛水平的能力。此外，标准混合规则通常用于组合系统中溶液相和固相的非键合力场参数，以表示界面行为，但未经验证。作为规避这些问题的一种方法，作者展示了一种高效的高级采样方法（TIGER2A）在模拟鸡蛋清溶菌酶在晶体（110）高密度聚乙烯表面平面上的吸附中的应用。使用经过验证可代表该系统界面行为的力场参数进行模拟，以生成采样状态的玻尔兹曼加权系综。然后使用内部开发的聚类分析方法对所得的采样状态系综进行分析，以根据执行的采样量预测蛋白质在表面上最可能的取向和构象，由此能够计算吸附状态之间的自由能差。此外，通过进行两组独立的TIGER2A模拟并结合聚类分析，作者展示了一种估计给定采样量所达到的收敛程度的方法。这些模拟结果表明，这些方法能够预测吸附蛋白质最可能的取向和构象，并且与使用标准CHARMM力场参数化来表示界面处的分子行为相比，使用我们经过验证的界面力场参数集能更接近现有实验结果。
