To determine the bioactive conformation required to bind with receptor aIIbb3, the peptide sequence RIPRGDMP from Kistrin was inserted into CDR 1 loop region of REI protein, resulting in REI-RGD34. The activity of REI-RGD34 was observed to increase at higher temperature towards the receptor aIIbb3. It could be justified in either way: the modified complex forces the restricted peptide to adapt bioactive conformation or it unfolds the peptide in a way that opens its binding surface with high affinity for receptor. Here, we model the conformational preference of RGD sequence in RIPRGDMP at 25 and 42 °C using multiple MD simulations. Further, we model the peptide sequence RGD, PRGD and PRGDMP from kistrin to observe the effect of flanking residues on conformational sampling of RGD. The presence of flanking residues around RGD peptide greatly influenced the conformational sampling. A transition from bend to turn conformation was observed for RGD sequence at 42 °C. The turn conformation shows pharmacophoric parameters required to recognize the receptor aIIbb3. Thus, the temperaturedependent activity of RIPRGDMP when inserted into the loop region of REI can be explained by the presence of the turn conformation. This study will help in designing potential antagonist for the receptor aIIbb3.

中文翻译：

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来自Kistrin的某些基于RGD的肽的分子动力学模拟提供了对REI-RGD34蛋白在更高温度下更高活性的了解。

为了确定与受体aIIbb3结合所需的生物活性构象，将来自Kistrin的肽序列RIPRGDMP插入REI蛋白的CDR 1环区域，得到REI-RGD34。观察到REI-RGD34的活性在较高温度下对受体aIIbb3增加。可以用任何一种方法证明其合理性：修饰的复合物迫使受限制的肽适应生物活性构象，或者以打开其结合表面且对受体具有高亲和力的方式展开肽。在这里，我们使用多个MD模拟对RIPRGDMP中RGDRGDMP在25和42°C下的构象偏好进行建模。此外，我们模拟了来自麒麟蛋白的肽序列RGD，PRGD和PRGDMP，以观察侧翼残基对RGD构象采样的影响。RGD肽周围的侧翼残基的存在极大地影响了构象采样。在42°C下观察到RGD序列从弯曲构型到转弯构型的过渡。转构象显示识别受体aIIbb3所需的药效学参数。因此，当插入到REI的环区域中时，RIPRGDMP的温度依赖性活性可以通过转弯构象的存在来解释。这项研究将有助于设计受体aIIbb3的潜在拮抗剂。RIPRGDMP插入REI的环区时，其温度依赖性活性可以通过存在转弯构象来解释。这项研究将有助于设计受体aIIbb3的潜在拮抗剂。RIPRGDMP插入REI的环区时，其温度依赖性活性可以通过存在转弯构象来解释。这项研究将有助于设计受体aIIbb3的潜在拮抗剂。