Análise in silico do complexo YCBB-PBP5 mediador de resistência a β-Lactâmicos

Abstract

The resistance mechanism mediated by L,D transpeptidase YcbB complexed with PBP5 in Escherichia coli allows a continuation of cell wall synthesis even in the presence of β-lactam antibiotics, enabling the survival of the bacteria even under cellular stress. Asking for an increase in the number of cases of bacterial resistance to the treatments available, the need to develop a better understanding of the mechanisms of resistance and, consequently, develop effective pharmacological solutions becomes evident. The aim of the study is to evaluate, through computer simulation techniques based on Density Functional Theory (DFT) and using Conjugated Layer Molecular Fractionation (MFCC) as a methodology, as energetic specificities present in the interaction between YcbB-Meropenem complexes and PBP5-Meropenem, from the use of the crystal structures of these proteins and the application of tools inherent in the field of computer simulation. For the first complex, 38 amino acids were obtained while for the PBP5-Meropenem system 42 amino acids were analyzed. Most energetically more residues are part of the binding reinforcement and the amino acids with higher energy generate situated at a distance of up to 4 Å, in both complexes. The results obtained indicate greater interaction energy between meropenem and PBP5 through the interaction of residues THR243, HIS245, SER116, LYS242, GLY114 and SER139 which were the most important. While for the YcbB complex and meropenem the most relevant amino acids are SER526, TYR507, LEU431, ILE506, THR430 ARG407, TRP425, PRO428. The methods used to analyze these results are bold and efficient, and the results are provided as a theoretical basis for the development of new drugs.