Combining simulations and experiments for the molecular engineering of multifunctional collagen mimetic peptide-based materials.
Combining simulations and experiments for the molecular engineering of multifunctional collagen mimetic peptide-based materials.
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DOI：
10.1039/d0sm01562h
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发表时间：
2021-02-21
期刊：
影响因子：
3.4
通讯作者：
Kloxin AM
中科院分区：
文献类型：
--
作者：
Hilderbrand AM;Taylor PA;Stanzione F;LaRue M;Guo C;Jayaraman A;Kloxin AM
组装肽允许产生结构复杂的材料，其中氨基酸选择影响所得性质。我们提出了一个协同的实验和模拟的方法，通过掺入带电残基和反应处理的多功能胶原蛋白模拟肽（CMP）的热稳定性和组装检查天然和非天然氨基酸取代的影响。实验上，我们观察到包含带电残基显着降低了CMP三螺旋的熔融温度，并在包含反应性手柄后进一步不稳定。一个单一的CMP三重螺旋在明确的水的原子模拟显示增加的残留水平和螺旋结构的波动所造成的列入反应处理，但是，这些原子模拟不能用来预测CMP熔融转变的变化。粗粒（CG）模拟CMP在实验相关的解决方案条件下，定性地显示出相同的趋势，在CMP熔融转变温度与CMP设计的实验。这些模拟表明，当带电残基包括静电排斥显着不稳定的CMP三螺旋和额外的包括一个反应性手柄不显着改变熔融转变。基于来自实验和模拟两者的发现，序列设计被改进以增加CMP三螺旋热稳定性，并且反应性柄被用于将组装的CMP并入共价交联的水凝胶内。总的来说，建立了一种独特的方法，用于在合成前预测各种序列的CMP三螺旋的稳定性，为序列设计提供分子见解，以创建散装纳米结构的软生物材料。
Assembling peptides allow the creation of structurally complex materials, where amino acid selection influences resulting properties. We present a synergistic approach of experiments and simulations for examining the influence of natural and non-natural amino acid substitutions via incorporation of charged residues and a reactive handle on the thermal stability and assembly of multifunctional collagen mimetic peptides (CMPs). Experimentally, we observed inclusion of charged residues significantly decreased the melting temperature of CMP triple helices with further destabilization upon inclusion of the reactive handle. Atomistic simulations of a single CMP triple helix in explicit water showed increased residue-level and helical structural fluctuations caused by the inclusion of the reactive handle; however, these atomistic simulations cannot be used to predict changes in CMP melting transition. Coarse-grained (CG) simulations of CMPs at experimentally relevant solution conditions, showed, qualitatively, the same trends as experiments in CMP melting transition temperature with CMP design. These simulations show that when charged residues are included electrostatic repulsions significantly destabilize the CMP triple helix and that an additional inclusion of a reactive handle does not significantly change the melting transition. Based on findings from both experiments and simulations, the sequence design was refined for increased CMP triple helix thermal stability, and the reactive handle was utilized for the incorporation of the assembled CMPs within covalently crosslinked hydrogels. Overall, a unique approach was established for predicting stability of CMP triple helices for various sequences prior to synthesis, providing molecular insights for sequence design towards the creation of bulk nanostructured soft biomaterials.
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