Shu Mao, Cheng Xiaoming, Zhang Yunru, Wang Yuanqiang, Lin Yong, Wang Li, Lin Zhihua
School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, PR China.
Protein Pept Lett. 2011 Dec;18(12):1233-43. doi: 10.2174/092986611797642706.
In this study, physicochemical scale (P-scale), was recruited as a novel set of physicochemical descriptors derived from component analysis on four short of physicochemical properties variables (hydrophobic, electronic, steric and hydrogen bond contribution) of 20 coded amino acids, By using partial least squares (PLS), we applied P-scale for the study of quantitative structure activity relationship models (QASRs) on three angiotensin I converting enzyme (ACE) inhibitory peptides datasets (58 dipeptides, 55 tripeptides, and 50 tetrapeptides).The results of QSARs were superior to that of the earlier studies, with correlation coefficient (r(2)) and cross-validated(q(2)) equal to 0.902, 0.86; 0.985, 0.951 and 0.872, 0.77, respectively. By analysis, hydrophobic and steric properties of ACE-inhibitory peptide sequences play important roles in their bioactivities, and novel peptide sequence could be designed based on these properties of the amino acid residues. These results showed that P-scale descriptors can well represent the peptide sequence. Furthermore, the robust models show that P-scale descriptors can be further expanded for polypeptides and can serve as a useful quantitative tool for the rational drug design and discovery.
在本研究中，物理化学量表（P量表）被用作一组新的物理化学描述符，它源自对20种编码氨基酸的四种物理化学性质变量（疏水、电子、空间和氢键贡献）进行的成分分析。通过使用偏最小二乘法（PLS），我们将P量表应用于三个血管紧张素I转化酶（ACE）抑制肽数据集（58种二肽、55种三肽和50种四肽）的定量构效关系模型（QSARs）研究。QSARs的结果优于早期研究，相关系数（r²）和交叉验证系数（q²）分别为0.902、0.86；0.985、0.951和0.872、0.77。通过分析可知，ACE抑制肽序列的疏水和空间性质在其生物活性中起重要作用，并且可以基于氨基酸残基的这些性质设计新的肽序列。这些结果表明，P量表描述符能够很好地表征肽序列。此外，稳健的模型表明，P量表描述符可进一步扩展用于多肽，并且可作为合理药物设计与发现的有用定量工具。
