Empirical estimation of local dielectric constants: Toward atomistic design of collagen mimetic peptides.
Empirical estimation of local dielectric constants: Toward atomistic design of collagen mimetic peptides.
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DOI：
10.1002/bip.22644
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发表时间：
2015-07
期刊：
影响因子：
2.9
通讯作者：
Nanda V
中科院分区：
文献类型：
--
作者：
Pike DH;Nanda V
蛋白质能量学建模的关键挑战之一是溶剂相互作用的处理。这在多肽的情况下尤其重要，其中大部分分子由于其小尺寸而高度暴露于溶剂。在这项研究中，我们开发了一种基于原子极化率的加性模型估计局部介电常数的经验方法。计算值与报道的一系列金黄色葡萄球菌核酸酶突变体的表观介电常数相符。计算出的常数用于确定筛选对库仑相互作用的影响，并确定基于改进的广义玻恩模型的溶剂化贡献。这些术语被整合到蛋白质建模平台protCAD中，并以实验确定的稳定性可用的胶原模拟肽数据集为基准。利用原子性蛋白质模型和加性原子极化率假设计算局部介电常数是一种快速且潜在有用的方法，可用于多肽的计算设计中，以改进静电和溶剂化计算。
One of the key challenges in modeling protein energetics is the treatment of solvent interactions. This is particularly important in the case of peptides, where much of the molecule is highly exposed to solvent due to its small size. In this study, we develop an empirical method for estimating the local dielectric constant based on an additive model of atomic polarizabilities. Calculated values match reported apparent dielectric constants for a series of Staphylococcus aureus nuclease mutants. Calculated constants are used to determine screening effects on Coulombic interactions and to determine solvation contributions based on a modified Generalized Born model. These terms are incorporated into the protein modeling platform protCAD, and benchmarked on a data set of collagen mimetic peptides for which experimentally determined stabilities are available. Computing local dielectric constants using atomistic protein models and the assumption of additive atomic polarizabilities is a rapid and potentially useful method for improving electrostatics and solvation calculations that can be applied in the computational design of peptides.