Stochastic-based descriptors studying biopolymers biological properties: Extended MARCH-INSIDE methodology describing antibacterial activity of lactoferricin derivatives

Lactoferricin are a number of related peptides derived from the enzymatic cleavage of lactoferrin, an iron‐binding protein. These peptides, and other peptides derived from them by simple amino acid substitutions, have shown interesting antibacterial activity. In this paper we applied the MARCH‐INSIDE methodology extended to peptide and proteins, to a QSAR study related to antibacterial activity of 31 derivatives of lactoffericin against E. Coli and S. Aureus by means of Linear Discriminant (LDA) and Multiple Linear Regression Analysis (MLR). In the case of LDA we obtained models that classify correctly more than 80% of all cases (85.7% for E. Coli antibacterial activity and 83.9 for S. Aureus). With the application of a Leave‐One‐Out Cross Validation Procedure, the percentage of good classification of both classification models remained near the above reported values (87.1% for E. Coli antibacterial activity and 83.9 for S. Aureus). We obtained several linear regression models taking into account total and local descriptors. The inclusion of those local descriptors improved the correlation parameters, the statistical quality, and the predictive power of the former model obtained only with total descriptors. The best models explained more than 80% of the experimental variance in the antimicrobial activity of those compounds. These results are comparable with those reported previously by Strom (Strom, M. B.; Rekdal, O.; Svendesen, J. S. J Peptide Res 2001, 57, 127–139.) and Tore‐Lejon (Lejon, T.; Strom, M.; Svendsen, S. J Protein Sci 2001, 7, 74–78.; Lejon, T.; Svendsen J. S.; Haug, B. E. J Peptide Sci 2002, 8, 302–306.) in a smaller dataset applying Z‐scales and volume‐based descriptors and PLS as statistical techniques. © 2005 Wiley Periodicals, Inc. Biopolymers, 2005