Investigation of the activity of different antimicrobial agents on streptococcus mutans sortase A by molecular method

Tooth decay is a common chronic disease that affects half of the world's population significantly causing pain, tooth loss, malnutrition and anxiety. Streptococcus mutans (S.mutans), a gram-positive bacteria, is considered the main pathogen of the tooth decay. Sortase A (SrtA) enzyme, one of the surface proteins of S.mutans, is a potential target in the development of antimicrobial and caries prevention agents to prevent infections associated with biofilm formation. In this study, by using molecular modeling methods to elucidate the inhibition mechanism of S.mutans SrtA enzyme at the molecular level and to reveal its basic structural features, it is aimed to determine the inhibitors that are more effective and have less side effects than existing inhibitors and to shed light on experimental studies. In this direction, in the first stage; the 3-dimensional structure of the target enzyme and interaction sites where inhibitors can show binding affinity were determined. In step 2, chemical compounds for S. mutans SrtA enzyme inhibition were screened through databases. In step 3, these compounds that were screened were evaluated for pharmacokinetics. In step 4, the free binding energy and inhibition coefficient were calculated by applying the molecular docking method between the pharmacokinetically suitable compounds and the target enzyme structure. At the last stage, amino acids that play a role in the enzyme-ligand interaction mechanism have been enlightened at the molecular level. As a result of the screening, 102 compounds were identified for S.mutans SrtA enzyme inhibition. Chlorhexidine (CHX) with known antibacterial effect on S.mutans was determined as a positive control. According to molecular docking results, 6 compounds (78, 10, 75, 12, 17, 97) on S.mutans SrtA enzyme had higher free binding energy (-7.18, -6.59, -6.53, -6.47, -6.43, -6.39 kcal/mol, respectively) than positive control CHX (-6.29 kcal/mol) showed more effective binding affinity. In addition, these active compounds were found to be more pharmacokinetically suitable than CHX and formed a strong chemical interaction with Arg213 and Cys205 amino acids, which have an important role in the biological activity of the SrtA enzyme. Thanks to this work enabled the development of more effective and specific inhibitors against the SrtA enzyme for the prevention of tooth decay by testing many chemical compounds more rapidly. Keywords: Enzyme inhibition, molecular docking, Streptococcus mutans, Sortase A, tooth decay