Modeling of peptide adsorption interactions with a poly(lactic acid) surface.
Modeling of peptide adsorption interactions with a poly(lactic acid) surface.
复制标题
与聚（乳酸）表面的肽吸附相互作用的建模。
DOI：
10.1021/la802588n
复制
发表时间：
2008-12-16
期刊：
影响因子：
--
通讯作者：
Latour RA
中科院分区：
文献类型：
--
作者：
O'Brien CP;Stuart SJ;Bruce DA;Latour RA
植入材料和器械的生物相容性取决于植入后立即吸附到材料表面的蛋白质层的构象、取向和组成，因此了解这种吸附的蛋白质层对于植入材料的严格和有条不紊的设计至关重要。在这项研究中，采用新的分子动力学技术，以确定在自由能的变化，为溶剂化的九个残基的肽（GGGG-K-GGGG）的结晶聚乳酸表面的吸附，努力阐明的基本机制，管理蛋白质吸附。这个系统，像许多其他系统一样，涉及两种不同类型的采样问题：空间采样问题，这是由于熵效应在自由能分布中产生障碍而产生的，以及构象采样问题，这是由于势能景观中的障碍而产生的。在一个两步的过程中，解决每个采样问题，反过来，有偏见的副本交换分子动力学的技术进行了改进和应用，以克服这些采样问题，并使用分子模拟提供的细节的原子水平上的信息，量化和表征肽和相关的生物材料表面之间的相互作用。这些模拟的结果预测了相当强的吸附响应，吸附自由能为-2.5 ± 0.6 kcal/mol（平均值±95%置信区间），吸附主要是由于肽的非极性基团与PLA表面之间的疏水相互作用。作为一个更大的和正在进行的努力，包括模拟和实验研究的一部分，这项工作有助于将生物材料工程从一个由试错为主的目标，这是由原子级的理解发生在组织生物材料界面的相互作用。
The biocompatibility of implanted materials and devices is governed by the conformation, orientation, and composition of the layer of proteins that adsorb to the surface of the material immediately upon implantation, so an understanding of this adsorbed protein layer is essential to the rigorous and methodical design of implant materials. In this study, novel molecular dynamics techniques were employed in order to determine the change in free energy for the adsorption of a solvated nine-residue peptide (GGGG-K-GGGG) to a crystalline polylactide surface in an effort to elucidate the fundamental mechanisms that govern protein adsorption. This system, like many others, involves two distinct types of sampling problems: a spatial sampling problem, which arises due to entropic effects creating barriers in the free energy profile, and a conformational sampling problem, which occurs due to barriers in the potential energy landscape. In a two-step process that addresses each sampling problem in turn, the technique of biased replica exchange molecular dynamics was refined and applied in order to overcome these sampling problems and, using the information available at the atomic level of detail afforded by molecular simulation, both quantify and characterize the interactions between the peptide and a relevant biomaterial surface. The results from these simulations predict a fairly strong adsorption response with an adsorption free energy of -2.5 ± 0.6 kcal/mol (mean ±95% confidence interval), with adsorption primarily due to hydrophobic interactions between the nonpolar groups of the peptide and the PLA surface. As part of a larger and ongoing effort involving both simulation and experimental investigations, this work contributes to the goal of transforming the engineering of biomaterials from one dominated by trial-and-error to one which is guided by an atomic-level understanding of the interactions that occur at the tissue-biomaterial interface.
登录
查看更多内容
影响因子：
3
作者：
KUMAR, S;ROSENBERG, JM;KOLLMAN, PA
通讯作者：
KOLLMAN, PA
影响因子：
2.9
作者：
HOOVER, WG
通讯作者：
HOOVER, WG
影响因子：
1.7
作者：
Martyna, GJ;Tuckerman, ME;Klein, ML
通讯作者：
Klein, ML
影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML