Impact of collagen-like peptide (CLP) heterotrimeric triple helix design on helical thermal stability and hierarchical assembly: a coarse-grained molecular dynamics simulation study.
Impact of collagen-like peptide (CLP) heterotrimeric triple helix design on helical thermal stability and hierarchical assembly: a coarse-grained molecular dynamics simulation study.
复制标题
胶原样肽（CLP）异三聚体三螺旋设计对螺旋热稳定性和分层组装的影响：粗粒度分子动力学模拟研究。
作者：
胶原样肽（Collagen-like Peptides，CLP）是一类多功能的生物材料，由于其可分级组装和可调节的理化性质，近年来引起了生物材料界的广泛关注。在这项工作中，我们提出了一个计算研究，链接CLP异源三聚体的热稳定性的三螺旋和自组装成纤维状聚集体和网状网络的设计。与同源三聚体螺旋不同，本研究中的CLP异源三聚体三螺旋由不同链长的CLP链组成，这些链长导致具有可用氢键基团的“粘性”末端。CLP异源三聚体的一端或两端的这些“粘性”末端然后促进螺旋间氢键，导致自组装成原纤维（簇）和交联网络。我们考虑的情况下，三个粘性末端长度-两个，四个和六个重复单元-完全存在于一端或分裂的CLP异源三聚体的两端之间。我们观察到在CLP异源三聚体熔融曲线产生粗粒Langevin动力学模拟在低CLP浓度，增加粘性末端长度的结果在较低的熔融温度为一个和两个粘性结束CLP设计。在更高的CLP浓度，我们观察到非单调的趋势，簇的大小与增加的粘性末端长度与一个粘性末端，但不是两个粘性末端与相同数量的可用氢键基团作为一个粘性末端;这种非单调性源于形成转向结构稳定的氢键在单一的粘性末端的粘性末端长度大于四个重复单元。随着CLP浓度的增加，异源三聚体也形成具有增加的粘性末端长度的交联网络，其中最小粘性末端长度为观察渗滤所需的四个重复单元。总的来说，这项工作通知设计的热响应性，基于肽的生物材料与所需的形态，使用链长度和分散性作为一个手柄，用于调整热稳定性和超分子结构的形成。
Collagen-like peptides (CLP) are multifunctional materials garnering a lot of recent interest from the biomaterials community due to their hierarchical assembly and tunable physicochemical properties. In this work, we present a computational study that links the design of CLP heterotrimers to the thermal stability of the triple helix and their self-assembly into fibrillar aggregates and percolated networks. Unlike homotrimeric helices, the CLP heterotrimeric triple helices in this study are made of CLP strands of different chain lengths that result in ‘sticky’ ends with available hydrogen bonding groups. These ‘sticky’ ends at one end or both ends of the CLP heterotrimer then facilitate inter-helix hydrogen bonding leading to self-assembly into fibrils (clusters) and percolated networks. We consider the cases of three sticky end lengths - two, four, and six repeat units - present entirely on one end or split between two ends of the CLP heterotrimer. We observe in CLP heterotrimer melting curves generated using coarse grained Langevin dynamics simulations at low CLP concentration that increasing sticky end length results in lower melting temperatures for both one and two sticky ended CLP designs. At higher CLP concentrations, we observe non-monotonic trends in cluster sizes with increasing sticky end length with one sticky end but not for two sticky ends with the same number of available hydrogen bonding groups as the one sticky end; this nonmonotonicity stems from the formation of turn structures stabilized by hydrogen bonds at the single, sticky end for sticky end lengths greater than four repeat units. With increasing CLP concentration, heterotrimers also form percolated networks with increasing sticky end length with a minimum sticky end length of four repeat units required to observe percolation. Overall, this work informs the design of thermoresponsive, peptide-based biomaterials with desired morphologies using strand length and dispersity as a handle for tuning thermal stability and formation of supramolecular structures.
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影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
影响因子：
5.5
作者：
Gautieri, Alfonso;Russo, Antonio;Buehler, Markus J.
通讯作者：
Buehler, Markus J.
影响因子：
2.7
作者：
Buehler, Markus J.
通讯作者：
Buehler, Markus J.
影响因子：
7.4
作者：
Dunshee, Lucas C.;Sullivan, Millicent O.;Kiick, Kristi L.
通讯作者：
Kiick, Kristi L.
DOI：
10.1073/pnas.0800291105
发表时间：
2008-06-24
影响因子：
11.1
作者：
Cejas, Mabel A.;Kinnney, William A.;Maryanoff, Bruce E.
通讯作者：
Maryanoff, Bruce E.