Uso de abordagens computacionais integradas para obtenção e caracterização de peptídeos antimicrobianos a partir de inibidores de proteases de plantas

Abstract

Serious bacterial infections are a global health issue, and plant protease inhibitors have the ability to inhibit or regulate proteases involved in the progression of several diseases. The aim of this work was to use computational methods in an integrated manner to discover antimicrobial peptides with potential for future clinical use, from plant protease inhibitors. For this, two approaches were used: in the first methodology, the peptides were generated from the hydrolysis of the amino acid sequence of the inhibitors and in the second through the prospecting of fragments with antimicrobial potential based on conserved regions. To evaluate the antimicrobial potential, the average scores of the CAMPR4, AI4AMP and HydrAMP platforms were used, and with the promising analyzes, libraries of variants were constructed using the Scramble platform to broadly evaluate the potential of these peptides. In addition, characterizations were performed regarding the physicochemical parameters with the aid of tools such as APD3, Heliquest, Expasy; Biological parameters such as antigenic, hemolytic, toxic potential, biofilm inhibition capacity, antioxidant and enzymatic susceptibility of the peptides were analyzed through platforms such as AnOxPP, HemoPI2.0, ToxinPred3; in the pharmacokinetic parameters, absorption by the human intestine and metabolism by CYP450 enzyme isoforms were evaluated through the ADMETSar platform; structural characteristics were also evaluated through Pepfold3.5. As a result, a total of 17 (7.32%) peptides and 24 (40%) variants with antimicrobial potential were obtained in the first approach; in the second, the results found were 6 (100%) and 17 (85%) analyzed with antimicrobial potential, respective to the peptides and their variants; All of these 64 peptides were characterized according to the parameters already mentioned. It is expected to offer important information for the use of peptides derived from plant protease inhibitors as possible candidates in in vitro and in vivo tests for clinical use.