Proteo-chemometrics analysis of MSH peptide binding to melanocortin receptors
Proteo-chemometrics analysis of MSH peptide binding to melanocortin receptors
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DOI：
10.1093/protein/15.4.305
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发表时间：
2002-04-01
期刊：
影响因子：
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通讯作者：
Wikberg, JES
中科院分区：
文献类型：
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作者：
Prusis, P;Lundstedt, T;Wikberg, JES
使用新型蛋白质化学计量学建模方法对已发表的六种黑皮质素肽与野生型和嵌合黑皮质素 MC1/MC3 受体结合的数据进行了分析。嵌合受体和肽使用二元描述符进行编码，并用于与肽与受体结合的亲和力或选择性的实验数据相关联。使用潜在结构的偏最小二乘投影（PLS）实现相关性，并获得统计上有效的模型。通过添加交叉项和应用正交信号校正，进一步改进了模型。使用外部预测验证模型，其中一半数据被排除在建模之外。使用 PLS 系数图对结果的解释表明，黑皮质素的结合袋位于黑皮质素受体的第一、第二、第三、第六和第七跨膜区域之间，与之前的黑皮质素与黑皮质素受体相互作用的三维模型非常一致。此外，对肽描述符之间交叉项的分析表明，蛋白质化学计量学模型能够区分影响结合亲和力和选择性的肽构象空间的差异。
The published data for six melanocortin peptides binding to wild-type and chimeric melanocortin MC1/MC3 receptors were analysed using the novel proteo-chemometrics modelling approach. The chimeric receptors and the peptides were coded using binary descriptors and used to correlate with the experimental data for affinity or selectivity for peptides binding to receptors. Correlations were achieved using partial least squares projection to latent structures (PLS) and statistically valid models were obtained. The models were further improved by adding cross-terms and applying orthogonal signal correction. The models were validated using external prediction, with half of the data being excluded from the modelling. Interpretation of the results using PLS coefficient plots revealed that the binding pocket for the melanocortins is located between the first, second, third, sixth and seventh transmembrane regions of the melanocortin receptors, in good agreement with previous three-dimensional models for the interactions of melanocortins with melanocortin receptors. Further, analysis of cross-terms between peptide descriptors indicated that the proteo-chemometrics modelling is able to distinguish between differences in the conformational space of the peptides that affect binding affinity and selectivity.