1st International and 10th National Iranian Conference on Bioinformatics
Home Accepted Papers
Homology modeling of FimH protein of Klebsiella pneumoniae :a key protein in bacterial pathogenesis
Paper ID : 1050-ICB10
Authors:
Fahimeh Mazroo *1, Mohamad Reza Dayer2, Fatemeh Khademimoghadam2
1Department of Biology, Faculty of Science, Kherad Institute of Higher Education
2Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
Abstract:
Klebsiella pneumoniae, as an important gram-negative pathogen causes urinary tract and respiratory infections which leads to large numbers of cases each year. One of the main factors involved in the pathogenicity of this bacterium is the FimH protein [1, 2]. This protein binds the bacterium to the host mucosal tissue, which leads to colonizing and multiplying the pathogen in that site and eventually inhibiting the host immune system [3, 4].
In this study, the tertiary structure of FimH protein of Klebsiella pneumoniae was predicted by homology modeling carried out by MODELLER software (Version 9.15). Two models (M1 and M2) were selected as output models for further analysis. After energy minimization of the models, their validation was checked by the analysis of the second structure (Ramachandran diagram), z-score, energy level, protein binding site, and docking experiments using mannose and FimH antagonist (alpha-D-mannopyranoside) as ligands.
Ramachandran plot showed that more than 92% of amino acids of M1 and M2 are in acceptable regions and their energy level analysis confirmed that they had appropriate structures. otherwise, the values for M1 and M2 in the Z-score plot were, -2.65 and -2.08 respectively. The values matched the experimentally determined values for the X-ray structures. It is noted that 21 possible active sites in FimH protein were identified by predicting protein binding sites. Finally, the docking results showed that binding energies of mannose to M1 and M2 were -195.45, -201.81 kJ/mol respectively while the binding energies of alpha-D-mannopyranoside to M1 and M2 were 310.45, -282.23 kJ/mol respectively.
In conclusion, our findings indicate that M1 model contrast to M2 seems to be a better model for further studies as FimH structure to control the pathogenicity of Klebsiella pneumoniae via drug design.
Keywords:
: Homology Modelling, K. pneumoniae, FimH, Structure Analysis
Status : Paper Accepted (Poster Presentation)