IDENTIFICATION OF THERAPEUTIC TARGETS FOR COMPUTER-BASED DESIGN OF DRUGS AGAINST BACTERIA CONTAINING THE PILT PROTEIN

摘要

The present invention relates to a method for identifying target regions at the interface of the monomers that form the PilT protein, with the aim of designing molecules potentially useful for compromising the activity of this protein, thus controlling infectious processes. The method is characterised by the following steps: (i) selection of at least one constitutive amino acid sequence of the PilT monomer; (ii) development of a three-dimensional computer model of the PilT homohexamer structure; (iii) computer analysis to determine the interface-forming amino acid residues (IFR) and the physico-chemical and structural characteristics thereof for all chains of the thus generated hexameric complex templates; (iv) selection of the regions to be used as therapeutic targets (and preferred therapeutic targets) at the monomer interface, on the basis of the intensity of predetermined parameters; (v) computer modelling for designing molecules that are potentially capable of binding to and/or interacting with monomer target regions. In particular, some of the main uses of this technology consist in the control of Xylella fastidiosa bacteria, the etiologic agent of citrus variegated chlorosis (CVC) and Pierce's disease.