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

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 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.

Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
Additional Information: This is an open-access article, which permits unrestricted use, distribution, and reproduction in any medium, for non-commercial purposes, provided the original author and source are credited.
Uncontrolled Keywords: parition coefficient,logP,peptides,octanol,biphasic system,QSAR
Publication ISSN: 0973-2063
Last Modified: 30 Sep 2024 10:05
Date Deposited: 09 Jul 2014 11:00
Full Text Link:
Related URLs: http://www.bioi ... net/001/001.htm (Publisher URL)
PURE Output Type: Article
Published Date: 2006
Authors: Thompson, Sarah J.
Hattotuwagama, Channa K.
Holliday, John D.
Flower, Darren R. (ORCID Profile 0000-0002-8542-7067)

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