Homology modeling of FimH protein of Klebsiella pneumoniae :a key protein in bacterial pathogenesis

Klebsiella pneumoniae, as an important gram-negative pathogen causes urinary tract and respiratoryinfections which leads to large numbers of cases each year. One of the main factors involved in thepathogenicity of this bacterium is the FimH protein. This protein binds the bacterium to the host mucosaltissue, which leads to colonizing and multiplying the pathogen in that site and eventually inhibiting the hostimmune system.In this study, the tertiary structure of FimH protein of Klebsiella pneumoniae was predicted by homologymodeling carried out by MODELLER software (Version ۹.۱۵). Two models (M۱ and M۲) were selected asoutput models for further analysis. After energy minimization of the models, their validation was checked bythe analysis of the second structure (Ramachandran diagram), z-score, energy level, protein binding site, anddocking experiments using mannose and FimH antagonist (alpha-D-mannopyranoside) as ligands.Ramachandran plot showed that more than ۹۲% of amino acids of M۱ and M۲ are in acceptable regions andtheir energy level analysis confirmed that they had appropriate structures. otherwise, the values for M۱ andM۲ in the Z-score plot were, -۲.۶۵ and -۲.۰۸ respectively. The values matched the experimentally determinedvalues for the X-ray structures. It is noted that ۲۱ possible active sites in FimH protein were identified bypredicting protein binding sites. Finally, the docking results showed that binding energies of mannose to M۱and M۲ were -۱۹۵.۴۵, -۲۰۱.۸۱ kJ/mol respectively while the binding energies of alpha-D-mannopyranosideto M۱ and M۲ were ۳۱۰.۴۵, -۲۸۲.۲۳ kJ/mol respectively.In conclusion, our findings indicate that M۱ model contrast to M۲ seems to be a better model for furtherstudies as FimH structure to control the pathogenicity of Klebsiella pneumoniae via drug design.

کلیدواژه ها:

Homology Modelling ، K. pneumoniae ، FimH ، Structure Analysis