MOLECULAR MODELLING OF CONFORMATIONS OF NON TRIPLE HELICAL REGIONS OF COLLAGEN

我们已经研究了偏离三螺旋 内脯氨酸贫乏序列的聚脯氨酸-II（ppII）构象 胶原 该段GTPGPQGIAGQRGVV，称为P15，用作 细胞粘附肽： 它与细胞上的受体结合并促进这些受体的分化。 细胞 衍生自P15的小肽以类似的方式起作用。 有许多实际应用的研究有关， 这些肽，因为诱导细胞结合的能力， 分化与伤口愈合、组织修复和组织损伤有关。 设计医疗和牙科假体。 我们的最终目标是 设计用于生物医学应用的非肽化合物， 模拟P15活性核心的结构和生物活性 和P15衍生肽。这个核心似乎是 异亮氨酸-丙氨酸。 我们已经研究了β-弯曲可以 与天然胶原蛋白分子相匹配。 特别是，我们研究了 中央GIAG处的弯曲如何能够适应胶原蛋白， 破坏其侧翼区的构象， 搁浅。 我们发现，使用图形建模和分子 力学，在GIAG的一个弯曲，被两种不同类型的 延伸构象，具有相同的端到端距离， 全pp-II P15序列，能量差异不显著 从pp-II构象。 最长的构象 QRGVV序列是具有phi和psi骨架扭转的序列 分别为大约-170度和165度的角度，而对于 GTPGPQ是最长的构象， 和psi大约等于-85和85度，因为 由脯氨酸残基引入的链中的扭结。 这 证明了三个模型的非pp-II的组合 构象可以适合胶原蛋白的相关链， 破坏了在分子链之外发现的链的pp-II构象， P15的末端。 MidasPlus和UCSF计算机的设施 图形实验室已被用于图形建模， 可视化的分子几何结构，用于制备P15在 理论计算的起始结构，以及 在这些计算之后监测结构。

We have investigated the deviation from the triple-helical polyproline-II (ppII) conformation of a proline-poor sequence within collagen. This segment, GTPGPQGIAGQRGVV, referred to as P15, acts as a cell adhesion peptide: It binds to receptors on cells and promotes differentiation of these cells. Small peptides derived from P15 act in a similar fashion. There are numerous practical applications of research relating to these peptides, since the ability to induce cell binding and differentiation is relevant to wound healing, tissue repair, and the design of medical and dental prostheses. Our ultimate goal is to design, for biomedical applications, a non-peptide compound that mimics the structure and biological activity of the active core of P15 and the P15-derived peptide s. This core appears to be the sequence Isoleucine-Alanine. We have examined ways in which a beta-bend could fit into a native collagen molecule. In particular, we have examined how a bend at the central GIAG could fit into collagen without disrupting the conformations of the flanking regions of the same strand. We have found, using graphical modelling and molecular mechanics, that a bend at GIAG, surrounded by two different types of extended conformations, has the same end-to-end distance as an all-pp-II P15 sequence, with an insignificant difference in energy from the pp-II conformation. The most extended conformation for the QRGVV sequence was found to be that with phi and psi backbone torsion angles of approximately -170 and 165 degrees, respectively, while for GTPGPQ the most extended conformation was found to be that with phi and psi approximately equal to -85 and 85 degrees, because of the kinks in the chain introduced by the proline residues. This demonstrates that the combination of the three modelled non-pp-II conformations can fit into the relevant strand of collagen without disrupting the pp-II conformation of the strand found beyond the termini of p15. MidasPlus and the facilities of the UCSF Computer Graphics laboratory have been used for graphical modelling and visualization of the molecular geometry, for preparing P15 in the starting structures for the theoretical calculations, and for monitoring the structures after these calculations.