Stochastic-Based Descriptors Studying Biopolymers Biological Properties: Extended MARCH-INSIDE Methodology Describing Antibacterial Activity of Lactoferricin Derivatives Ronal Ramos de Armas 1,2 Humberto Gonza ´ lez Dı ´az 1,3 Reinaldo Molina 1,4 Eugenio Uriarte 3 1 Chemical Bioactives Center, Central University of “Las Villas” 54830, Cuba 2 Department of Chemistry, Central University of “Las Villas” 54830, Cuba 3 Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela 15782, Spain 4 Universita ¨ t Rostock, FB Chemie, Albert-Einstein-Str. 3a, D 18059 Rostock, Germany Received 16 September 2004; revised 25 October 2004; accepted 27 October 2004 Published online 28 January 2005 in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/bip.20202 Abstract: 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 pre- dictive 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 Correspondence to: R. Ramos de Armas; email: ronalr@qf.uclv.edu.cu or ronal@medinews.com Biopolymers, Vol. 77, 247–256 (2005) © 2005 Wiley Periodicals, Inc. 247