An In Silico Study for the Identification of Novel Putative Compounds Against the Wild and Mutant Type Penicillin Binding Protein 2 of Neisseria Gonorrhoeae

Abstract

Penicillin-binding protein 2 (PBP2) is an enzyme crucial for cell wall biosynthesis during cell proliferation of N. gonorrhoeae. In the present work, the crystal structures of wild and mutant type PBP2 were analyzed to identify structural changes leading to antibiotic resistance. Other than these two targets, three other targets were generated by analyzing possible hot spots for mutations in PBP2. By using a reverse screening approach, fifteen molecules were screened and processed for ligand binding analysis with all five targets. The analysis of the above studies suggested that two compounds Guanosine 5’-diphosphate and Thymidine 3', 5’-diphosphate show the good binding affinity than Ceftriaxone and other compounds. Further, we have generated ten novel compounds using Ceftriaxone, Guanosine 5’-diphosphate, and Thymidine 3', 5’-diphosphate. To identify the novel findings, all novel compounds were docked against aforesaid five targets. The studies resulted in the finding of three best molecules that may be considered as suitable, potent, and generic inhibitors against N. gonorrhoeae other than Ceftriaxone.