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

我们正在研究束缚沃茨对 三螺旋构象的水溶液稳定性 （Pro-Pro-Gly）10（（PPG）10），胶原蛋白三联体的简单模拟物 螺旋。 对稳定这种分子的因素的了解可能 有助于智能聚合物和生物材料的设计。 我们 先前构建了（PPG）10中结合沃茨的模型，其中 在每个结合水和一对 不同多肽链上的骨架羰基。 沃茨 形成桥的位置在空间上拥挤，导致 不寻常的行为，如熔化温度的大幅增加 当水被氧化氘取代时，（PPG）10的。 我们现在 用分子动力学方法进一步验证了该模型的有效性 (MD)在明确的水分子浴中模拟（PPG）10， 研究上述水桥的形成， 任意位置的沃茨。 我们将监控动态行为， 百分比的占用率，以及在一个漫长的 仿真 我们已经看到了几种溶剂化现象，包括 我们的模型（入住率低于100%）和水合类型 显示在最近公布的晶体结构（PPG）10中。 我们 也在研究溶剂化作用对 由（Gly-Pro-Ala）10组成的三螺旋结构， （Gly-Ala-Pro）10和（Pro-Pro-[β-丙氨酸]）10。 MidasPlus和 UCSF计算机图形实验室的设施已被用于 将这些胶原模拟物建模为起始构象， 计算，用于观察由 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.