Thompson Sarah J, Hattotuwagama Channa K, Holliday John D, Flower Darren R
Edward Jenner Institute for Vaccine Research, High Street, Compton, Berkshire, RG20 7NN, UK.
Bioinformation. 2006 Nov 14;1(7):237-41. doi: 10.6026/97320630001237.
Peptides are of great therapeutic potential as vaccines and drugs. Knowledge of physicochemical descriptors, including the partition coefficient logP, is useful for the development of predictive Quantitative Structure-Activity Relationships (QSARs). We have investigated the accuracy of available programs for the prediction of logP values for peptides with known experimental values obtained from the literature. Eight prediction programs were tested, of which seven programs were fragment-based methods: XLogP, LogKow, PLogP, ACDLogP, AlogP, Interactive Analysis's LogP and MlogP; and one program used a whole molecule approach: QikProp. The predictive accuracy of the programs was assessed using r(2) values, with ALogP being the most effective (r( 2) = 0.822) and MLogP the least (r(2) = 0.090). We also examined three distinct types of peptide structure: blocked, unblocked, and cyclic. For each study (all peptides, blocked, unblocked and cyclic peptides) the performance of programs rated from best to worse is as follows: all peptides - ALogP, QikProp, PLogP, XLogP, IALogP, LogKow, ACDLogP, and MlogP; blocked peptides - PLogP, XLogP, ACDLogP, IALogP, LogKow, QikProp, ALogP, and MLogP; unblocked peptides - QikProp, IALogP, ALogP, ACDLogP, MLogP, XLogP, LogKow and PLogP; cyclic peptides - LogKow, ALogP, XLogP, MLogP, QikProp, ACDLogP, IALogP. In summary, all programs gave better predictions for blocked peptides, while, in general, logP values for cyclic peptides were under-predicted and those of unblocked peptides were over-predicted.
肽作为疫苗和药物具有巨大的治疗潜力。包括分配系数logP在内的物理化学描述符知识，对于预测性定量构效关系（QSAR）的开发很有用。我们利用从文献中获得的已知实验值，研究了用于预测肽的logP值的现有程序的准确性。测试了八个预测程序，其中七个程序是基于片段的方法：XLogP、LogKow、PLogP、ACDLogP、AlogP、Interactive Analysis's LogP和MlogP；还有一个程序使用了全分子方法：QikProp。使用r(2)值评估程序的预测准确性，其中AlogP最有效（r(2)=0.822），MLogP最无效（r(2)=0.090）。我们还研究了三种不同类型的肽结构：封闭型、非封闭型和环型。对于每项研究（所有肽、封闭型肽、非封闭型肽和环型肽），程序的性能从最佳到最差依次为：所有肽——AlogP、QikProp、PLogP、XLogP、IALogP、LogKow、ACDLogP和MlogP；封闭型肽——PLogP、XLogP、ACDLogP、IALogP、LogKow、QikProp、AlogP和MLogP；非封闭型肽——QikProp、IALogP、AlogP、ACDLogP、MLogP、XLogP、LogKow和PLogP；环型肽——LogKow、AlogP、XLogP、MLogP、QikProp、ACDLogP、IALogP。总之，所有程序对封闭型肽的预测更好，而一般来说，环型肽的logP值预测偏低，非封闭型肽的logP值预测偏高。
