identification of therapeutic targets for computational drug design against pilt protein bacteria

摘要

IDENTIFICATION OF THERAPEUTIC TARGETS FOR COMPUTER DESIGN OF DRUGS AGAINST PILT-GATED BACTERIA. The present invention relates to a method for identifying target regions existing at the interface of PilT protein constituent monomers with the aim of designing potentially applicable molecules in compromising the activity of this protein, thereby controlling infectious processes. The method is characterized by (i) selecting at least one PilT monomer constituent amino acid sequence; (ii) development of a three-dimensional computational model of PilT's homohexameric structure; (iii) computational analysis to determine the interface-forming amino acid (IFR) residues and their physicochemical and structural characteristics for all chains of the generated hexameric complex models; (iv) selecting the regions to be used as therapeutic targets (and preferred therapeutic targets) at the interface between monomers based on the intensity of certain parameters; (v) computational modeling for the design of molecules potentially capable of effecting linkages and / or interactions between target regions of monomers. Notably, some of the main applications of this technology are the fight against the bacterium Xylella fastidiosa, etiological agent of Citrus Variegated Chlorosis (CVC or Amarelinho), and Pierce's disease.