Objective:The objective of this study was to search for targeted small molecule inhibitors of Sortase A(SrtA)of Streptococcus mutans(S.mutans),and to provide an experimental basis for the exploration of novel and effective anti-caries drugs.Methods:Using the crystal structure of SrtA enzyme of S.mutans UA159(PDB code:4TQX)as the receptor and amino acid Cys205 as the covalent binding site,we screened potential small molecule compounds from the natural small molecule drug-like molecule libraries of the compounds using molecular covalent docking technology and ADMET drug-forming filtration.The study screened small molecule compounds that inhibit adhesion without antibacterial effect,as determined by the minimum inhibitory concentration(MIC)and bacterial adhesion experiments.The binding modes and stabilities of the small molecule compounds were verified through molecular dynamics simulation.Results:A total of 20 small molecule compounds were selected by molecular co-valent docking technology and ADMET druggability filtration,among which AK-968/40369373 and AK-968/40385877 inhibited the adhesion of S.mutans better than trans-chalcone,and the difference was statistically significant(P＜0.05).Molecular dynam-ics simulations confirmed that AK-968/40369373 and AK-968/40385877 could form stable covalent binding to SrtA.Conclusion:Virtual screening and validation are effective methods for selecting potential targeting inhibitors of SrtA.The small-molecule com-pounds AK-968/40369373 and AK-968/40385877 obtained in this study are expected to be used as small-molecule inhibitors tar-geting S.mutans SrtA.

Objective:The objective of this study was to search for targeted small molecule inhibitors of Sortase A(SrtA)of Streptococcus mutans(S.mutans),and to provide an experimental basis for the exploration of novel and effective anti-caries drugs.Methods:Using the crystal structure of SrtA enzyme of S.mutans UA159(PDB code:4TQX)as the receptor and amino acid Cys205 as the covalent binding site,we screened potential small molecule compounds from the natural small molecule drug-like molecule libraries of the compounds using molecular covalent docking technology and ADMET drug-forming filtration.The study screened small molecule compounds that inhibit adhesion without antibacterial effect,as determined by the minimum inhibitory concentration(MIC)and bacterial adhesion experiments.The binding modes and stabilities of the small molecule compounds were verified through molecular dynamics simulation.Results:A total of 20 small molecule compounds were selected by molecular co-valent docking technology and ADMET druggability filtration,among which AK-968/40369373 and AK-968/40385877 inhibited the adhesion of S.mutans better than trans-chalcone,and the difference was statistically significant(P＜0.05).Molecular dynam-ics simulations confirmed that AK-968/40369373 and AK-968/40385877 could form stable covalent binding to SrtA.Conclusion:Virtual screening and validation are effective methods for selecting potential targeting inhibitors of SrtA.The small-molecule com-pounds AK-968/40369373 and AK-968/40385877 obtained in this study are expected to be used as small-molecule inhibitors tar-geting S.mutans SrtA.