Title

On the hydrophobicity of peptides: Comparing empirical predictions of peptide log P values

Authors

Sarah J. Thompson1,², Channa K. Hattotuwagama¹, John D. Holliday ² and Darren R. Flower ¹*
 

Affiliation

¹ Edward Jenner Institute for Vaccine Research, High Street, Compton, Berkshire, RG20 7NN, UK; ² Dept. of Information Studies, University of Sheffield

Email

darren.flower@jenner.ac.uk; *Corresponding author

Phone

+44 1635 577954

Fax

+44 1635 577908

Article Type

Prediction Model

Date

received October 14, 2006; accepted November 02, 2006; published online November 14, 2006

Abstract

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 r² values, with ALogP being the most effective (r² = 0.822) and MLogP the least (r² = 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.

Keywords

partition coefficient; logP; peptides; octanol; biphasic system; QSAR  

Citation

Thompson et al., Bioinformation 1(7): 237-241 (2006)
 

Edited by

P. Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.