Theoretical Evaluation of Novel Thermolysin Inhibitors from Bacillus thermoproteolyticus. Possible Antibacterial Agents

Molecules

Karel Mena-Ulecia¹  Desmond MacLeod-Carey²  FernandoP. Miranda³  Emilio Lamazares⁴ 

[1] Departamento de Ciencias Biológicas y Químicas, Facultad de Recursos Naturales, Universidad Católica de Temuco, Ave. Rudecindo Ortega 02950, Temuco 4780000, Chile;Inorganic Chemistry and Molecular Materials Center, Instituto de Ciencias Químicas Aplicadas, Facultad de Ingeniería, Universidad Autónoma de Chile, El Llano Subercaseaux 2801, San Miguel, Santiago 8900000, Chile;Instituto de Fisiología, Facultad de Medicina, Universidad Austral de Chile, Valdivia 5090000, Chile;Pathophysiology Department, Biotechnology and Biopharmaceutical Laboratory, School of Biological Sciences, Universidad de Concepción, Victor Lamas 1290, P.O. Box 160-C, Concepción 4079386, Chile;

关键词: thermolysin;    antibacterial agents;    docking;    molecular dynamics;    MM-PBSA;    ADME-Tox;   

DOI  :  10.3390/molecules26020386

来源: DOAJ

【 摘 要 】

The search for new antibacterial agents that could decrease bacterial resistance is a subject in continuous development. Gram-negative and Gram-positive bacteria possess a group of metalloproteins belonging to the MEROPS peptidase (M4) family, which is the main virulence factor of these bacteria. In this work, we used the previous results of a computational biochemistry protocol of a series of ligands designed in silico using thermolysin as a model for the search of antihypertensive agents. Here, thermolysin from Bacillus thermoproteolyticus, a metalloprotein of the M4 family, was used to determine the most promising candidate as an antibacterial agent. Our results from docking, molecular dynamics simulation, molecular mechanics Poisson–Boltzmann (MM-PBSA) method, ligand efficiency, and ADME-Tox properties (Absorption, Distribution, Metabolism, Excretion, and Toxicity) indicate that the designed ligands were adequately oriented in the thermolysin active site. The Lig783, Lig2177, and Lig3444 compounds showed the best dynamic behavior; however, from the ADME-Tox calculated properties, Lig783 was selected as the unique antibacterial agent candidate amongst the designed ligands.

【 授权许可】

Unknown