Development of a Coarse-Grained Model of Collagen-Like Peptide (CLP) for Studies of CLP Triple Helix Melting
Development of a Coarse-Grained Model of Collagen-Like Peptide (CLP) for Studies of CLP Triple Helix Melting
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DOI：
10.1021/acs.jpcb.7b10916
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发表时间：
2018-02-15
影响因子：
3.3
通讯作者：
Jayaraman, Arthi
中科院分区：
文献类型：
--
作者：
Condon, Joshua E.;Jayaraman, Arthi
在本文中，我们提出了一种现象学粗粒度模型的发展，该模型代表单链胶原样肽（CLPs）以及CLP三螺旋。该模型开发的目标是实现CLP溶液和CLP与其他大分子共轭物的粗粒度分子模拟，并预测CLP熔点随不同CLP设计的趋势，即CLP长度和组成。由于CLP三螺旋结构主要由相邻链中氨基酸之间的氢键稳定，为了模拟CLP熔化，我们从最近的粗粒度（CG）模型中获得灵感，该模型用于捕获寡核苷酸内碱基对杂交中特定和定向的氢键相互作用，并在隐式水中再现已知的DNA熔化趋势与DNA序列和组成。在本文中，我们系统地描述了我们对这个原始CG模型所做的改变，然后表明这些改进再现了过去实验中看到的已知clp熔化趋势。具体来说，在实验相关浓度下的CLP溶液的CG模拟显示，随着CLP长度的增加，熔化温度升高，随着CLP中带电残基取代不带电残基的加入，熔化温度降低，这与过去的实验观察结果一致。最后，利用这种新的CLP CG模型，模拟了CLP三螺旋与弹性蛋白样肽（ELP）共轭的结果，再现了与过去实验中看到的ELP聚集趋势相同。
In this paper, we present the development of a phenomenological coarse-grained model that represents single strands of collagen-like peptides (CLPs) as well as CLP triple helices. The goal of this model development is to enable coarse grained molecular simulations of solutions of CLPs and conjugates of CLPs with other macromolecules and to predict trends in the CLP melting temperature with varying CLP design, namely CLP length and composition. Since the CLP triple helix is stabilized primarily by hydrogen bonds between amino acids in adjacent strands, for modeling CLP melting we get inspiration from a recent coarse-grained (CG) model that was used to capture specific and directional hydrogen-bonding interactions in base-pair hybridization within oligonucleotides and reproduced known DNA melting trends with DNA sequence and composition in implicit water. In this paper, we systematically describe the changes we make to this original CG model and then show that these improvements reproduce the known melting trends of CLPs seen in past experiments. Specifically, the CG simulations of CLP solutions at experimentally relevant concentrations show increasing melting temperature with increasing CLP length and decreasing melting temperature with incorporation of charged residues in place of uncharged residues in the CLP, in agreement with past experimental observations. Finally, results from simulations of CLP triple helices conjugated with elastin like peptides (ELPs), using this new CG model of CLP, reproduce the same trends in ELP aggregation as seen in past experiments.