Application of advanced sampling and analysis methods to predict the structure of adsorbed protein on a material surface
Application of advanced sampling and analysis methods to predict the structure of adsorbed protein on a material surface
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DOI：
10.1116/1.4983274
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发表时间：
2017-06-01
期刊：
影响因子：
2.1
通讯作者：
Latour, Robert A.
中科院分区：
文献类型：
--
作者：
Abramyan, Tigran M.;Hyde-Volpe, David L.;Latour, Robert A.
使用标准分子动力学模拟方法来预测蛋白质与材料表面的相互作用具有固有的局限性，即缺乏确定表面上吸附的蛋白质的最可能的构象和取向以及确定通过模拟获得的收敛水平的能力。此外，标准的混合规则通常适用于联合收割机的溶液和固相的系统的非键力场参数来表示界面行为，而无需验证。作为一种手段，以规避这些问题，作者证明了一个有效的先进的采样方法（TIGER 2A）的应用程序的模拟鸡蛋白溶菌酶的吸附结晶（110）高密度聚乙烯表面平面。进行模拟，以产生一个玻尔兹曼加权合奏的采样状态，使用力场参数，验证代表该系统的界面行为。然后使用内部开发的聚类分析方法分析所得到的采样状态的集合，以基于所进行的采样量来预测表面上蛋白质的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TIGER 2A模拟与聚类分析相结合，作者展示了一种方法来估计在给定的采样量下实现的收敛程度。从这些模拟的结果表明，这些方法使最可能的方向和构象的吸附蛋白质被预测，并使用我们验证的界面力场参数集提供了更接近的协议可用的实验结果相比，使用标准的CHARMM力场参数化，以代表在界面上的分子行为。(C)2017年美国真空学会。
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 of 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. (C) 2017 American Vacuum Society.