Idowu J Adeosun

Conference 2023 Presentation

Project title

Molecular modelling of SdiA protein by selected flavonoids and terpenes compounds to attenuate virulence in Klebsiella pneumoniae

Authors and Affiliations

Idowu Jesulayomi Adeosun1, Itumeleng Baloyi1, Aimen K. Aljoundi2, Elliasu Y. Salifu2, Mohammed Auwal Ibrahim3 and Sekelwa Cosa1

1. Department of Biochemistry, Genetics and Microbiology, University of Pretoria, Hatfield, South Africa
2. Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
3. Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria

Abstract

Background

Klebsiella pneumoniae is one of the perturbing multidrug resistant (MDR) and ESKAPE pathogens contributing to the mounting morbidity, mortality and extended rate of hospitalization. Its virulence, often regulated by quorum sensing (QS) reinforces the need to explore alternative and prospective antivirulence agents, relatively from plants secondary metabolites. Computer aided drug discovery using molecular modelling techniques offers advantage to investigate prospective drugs to combat MDR pathogens. Thus, this study employed virtual screening of selected terpenes and flavonoids from medicinal plants to interrupt the QS associated SdiA protein in K. pneumoniae to attenuate its virulence.

Methods

4LFU was used as a template to model the structure of SdiA. ProCheck, Verify3D,
Ramachandran plot scores, and ProSA-Web all attested to the model’s good quality. Since SdiA protein in K. pneumoniae leads to the expression of virulence, 31 prospective bioactive compounds were docked for antagonistic potential. The stability of the protein-ligand complex, atomic motions and inter-atomic interactions were further investigated through molecular dynamics simulations (MDS) at 100 ns production runs. The binding free energy was estimated using the molecular mechanics/poisson-boltzmann surface area (MM/PB SA). Furthermore, the drug-likeness properties of the studied compounds were validated.

Results

Docking studies showed phytol possesses the highest binding affinity (-9.205 kcal/mol) while glycitein had -9.752 kcal/mol highest docking score. The MDS of the protein in complex with the best-docked compounds revealed phytol with the highest binding energy of -44.2625 kcal/mol, a low root-mean-square deviation (RMSD) value of 1.54 Å and root-mean-square fluctuation (RMSF) score of 1.78 Å. Analysis of the drug-likeness properties prediction and bioavailability of these compounds revealed their conformed activity to lipinski’s rules with bioavailability scores of 0.55 F.

Conclusions

The studied terpenes and flavonoids compounds effectively thwart SdiA protein, therefore regulate inter- or intra cellular communication and associated virulence in Enterobacteriaceae, serving as prospective antivirulence drugs.