MOLECULAR MODELING OF SOLVATION OF (PRO PRO GLY)10 & RELATED COLLAGEN MIMETICS

我们正在调查束缚水对 三螺旋构象在水溶液中的稳定性 (Pro-Pro-Gly)10((PPG)10)，一个简单的胶原三联体的模拟物 螺旋。对稳定这种分子的因素的了解可能会 为智能聚合物和生物材料的设计做出贡献。我们 之前在(PPG)10中构建了束缚水模型，其中 在每个结合水和一对水之间形成桥式氢键 不同多肽链上的主链羰基。这片水域 形成桥梁的位置非常拥挤，导致 异常行为，如熔化温度大幅上升 (PPG)10，当水被氧化氢取代时。我们现在是 利用分子动力学进一步验证了该模型的有效性 (MD)(PPG)10在显式水分子浴中的模拟，以 从研究上述水桥的形成入手 任意位置的水域。我们将监控动态行为， 入住率，以及长时间跨度的生命周期 模拟。我们已经看到了几种溶剂化现象，包括 我们的模型(占有率低于100%)和水化类型 显示在最近发表的(PPG)10的晶体结构中。我们 也在研究溶剂化对分子相对稳定性的影响 由(Gly-Pro-Ala)10， (Gly-Ala-Pro)10和(Pro-Pro-[Beta-Alanine])10.MidasPlus和 加州大学旧金山分校计算机图形实验室的设施已用于 将这些胶原蛋白模拟物建模为起始构象 用于观察由以下原因产生的结构的计算 计算。

We are investigating the contribution of bound waters to the stability in aqueous solution of the triple-helical conformation of (Pro-Pro-Gly)10 ((PPG)10), a simple mimic of the collagen triple helix. An understanding of the factors stabilizing this molecule may contribute to the design of intelligent polymers and biomaterials. We previously constructed a model for bound waters in (PPG)10 in which bridging hydrogen bonds are formed between each bound water and a pair of backbone carbonyls on different polypeptide chains. The waters forming the bridges are in sterically crowded positions, leading to unusual behavior, such as a large increase in the melting temperature of (PPG)10 when water is replaced by deuterium oxide. We are now testing the validity of this model further by using molecular dynamics (MD) simulations of (PPG)10 in a bath of explicit water molecules, to study the formation of the aforementioned water bridges starting with waters in arbitrary locations. We will monitor the dynamic behavior, percent occupancy, and lifetime over the timespan of a long simulation. We have seen several solvation phenomena, including both our model (at less than 100% occupancy) and the types of hydration displayed in a recently published crystal structure of (PPG)10. We are also investigating solvation effects on the relative stability of triple-helical structures composed of (Gly-Pro-Ala)10, (Gly-Ala-Pro)10, and (Pro-Pro-[Beta-alanine])10. MidasPlus and the facilities of the UCSF Computer Graphics Laboratory have been used for modeling these collagen mimetics into starting conformations for calculations, for observing the structures resulting from calculations.