Investigations of binding mode insight in Salmonella typhi type-III secretion system tip protein (SipD): A molecular docking and MD simulation study

Abstract

Salmonella typhi is a Gram-negative pathogen that utilizes type three secretion systems (TTSS) to translocate virulence factors into host cells. This causes a wide variety of diseases mainly gastroenteritis and typhoid fever in both humans and animals. Salmonella invasive protein D (SipD) is a tip protein, attached to the needle protein and interacts with translocon complex. Exploring the molecular mechanisms of SipD may aid in better understanding about secretion, translocators and transmission of environmental signals of Salmonella. In this study, SipD sequence (Q56136) was retrieved from Uniprot for which three-dimensional (3D) structure was modelled with the help of I-TASSER server. The modelled structure was subjected to molecular docking using Glide. About 25 compounds of T3SS inhibitors were chosen after literature studies and docking was performed. It was evident that polyol product Caminoside A possessed (≤-5 kcal/mol) the best interaction with SipD and therefore this complex was subjected to molecular dynamic simulation for interaction stability analysis. The simulation results showed that Caminoside A binding was highly stable (life time of 80%) with SipD and Asn318 interaction was more significant for the protein-ligand complex stability. These results will provide new knowledge for the development of novel therapeutic strategies against Salmonella typhi.

Keywords

• Salmonella typhi
• Type-III secretion system
• SipD
• Caminoside A
• Molecular dynamics simulation