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首页> 外文期刊>Receptors and channels >Mapping the binding site of the small intestinal peptide carrier (PepT1) using comparative molecular field analysis.
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Mapping the binding site of the small intestinal peptide carrier (PepT1) using comparative molecular field analysis.

机译：使用比较分子场分析法绘制小肠肽载体（PepT1）的结合位点。

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摘要

The present study was undertaken to examine the relationship between chemical structure (steric and electrostatic fields) and affinity for the small intestinal oligopeptide carrier (PepT1) using comparative molecular field analysis (CoMFA), a three-dimensional approach towards building quantitative structure-activity relationships. Various biological activity parameters (Kt, Jmax, Pc) and molecular descriptors (CoMFA fields, isobutylalcohol/water distribution coefficients) were examined. The resulting field map provides information on the geometry of the binding site cavity and the relative weights of various properties in different site pockets for each of the substrates considered. The results indicate that carrier permeability (Pc), calculated as the ratio of the half-maximal concentration (Kt) and the maximal carrier flux (Jmax), is sensitive to composition, size and hydrophobicity of the ligands. The best model obtained showed a high correlation between the carrier permeability (Pc) and the steric (76.3% contribution) and electrostatic (23.7% contribution) molecular fields with a cross-validated r2 (q2) of 0.754. The model fitted the experimental data with a correlation coefficient of 0.993 and a standard error of 0.041, while the regression line between experimental and calculated Pc had a slope of 0.994 with an intercept of 0.009. These results lead to a better understanding of the molecular requirements for optimal drug-carrier interactions with the intestinal peptide transporter and offers a useful visual aid for designing new potentially interesting structures with affinity for the oligopeptide transporter PepT1.
机译：本研究旨在使用比较分子场分析（CoMFA）来研究化学结构（空间和静电场）与小肠寡肽载体（PepT1）亲和力之间的关系，该方法是建立定量结构与活性关系的三维方法。检查了各种生物活性参数（Kt，Jmax，Pc）和分子描述符（CoMFA场，异丁醇/水分配系数）。所得的场图提供了有关所考虑的每种底物的结合位点腔的几何形状以及不同位点袋中各种特性的相对权重的信息。结果表明，载流子渗透率（Pc），以半数最大浓度（Kt）与最大载流子流量（Jmax）之比计算，对配体的组成，大小和疏水性敏感。获得的最佳模型显示出载流子渗透率（Pc）与空间（贡献76.3％）和静电（贡献23.7％）分子场之间具有高度相关性，交叉验证的r2（q2）为0.754。该模型拟合的实验数据的相关系数为0.993，标准误差为0.041，而实验数据与计算出的Pc之间的回归线的斜率为0.994，截距为0.009。这些结果使人们更好地理解了与肠道肽转运蛋白进行最佳药物-载体相互作用的分子要求，并为设计与寡肽转运蛋白PepT1亲和的潜在的新结构提供了有用的视觉帮助。

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