Molecular Docking and Dynamics Simulation of Protein β-Tubulin and Antifungal Cyclic Lipopeptides

Abstract

To elucidate interactions between the antifungal cyclic lipopeptides iturin A, fengycin, and surfactin produced by Bacillus bacteria and the microtubular protein β-tubulin in plant pathogenic fungi (Fusarium oxysporum, Colletrotrichum gloeosporioides, Alternaria alternata, and Fusarium solani) in molecular docking and molecular dynamics simulations, we retrieved the structure of tubulin co-crystallized with taxol from the Protein Data Bank (PDB) (ID: 1JFF) and the structure of the cyclic lipopeptides from PubChem (Compound CID: 102287549, 100977820, 10129764). Similarity and homology analyses of the retrieved β-tubulin structure with those of the fungi showed that the conserved domains shared 84% similarity, and the root mean square deviation (RMSD) was less than 2 Å. In the molecular docking studies, within the binding pocket, residues Pro274, Thr276, and Glu27 of β-tubulin were responsible for the interaction with the cyclic lipopeptides. In the molecular dynamics analysis, two groups of ligands were formed based on the number of poses analyzed with respect to the RMSD. Group 1 was made up of 10, 100, and 500 poses with distances 0.080 to 0.092 nm and RMSDs of 0.10 to 0.15 nm. For group 2, consisting of 1000 poses, the initial and final distance was 0.1 nm and the RMSDs were in the range of 0.10 to 0.30 nm. These results suggest that iturin A and fengycin bind with higher affinity than surfactin to β-tubulin. These two lipopeptides may be used as lead compounds to develop new antifungal agents or employed directly as biorational products to control plant pathogenic fungi.

Efficacy of Phytochemicals Derived from Avicennia officinalis for the Management of COVID-19: A Combined In Silico and Biochemical Study

“…Previous findings have indicated that the presence of more polar metabolites, such as naphthoquinones and phenolics, can enhance the antioxidant activities of A. officinalis plant components [ 42 ]. A study also reported that this mangrove plant had a less toxic effect on Vero cell lines [ 43 ], which significantly supported our present investigation, in which the LC 50 value determined by the brine shrimp lethality was less than 250 µg/mL [ 44 ].…”

Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation

“…Trajectories analyses were performed using the CPPTRAJ modules (Roe & Cheatham, 2013. Authors analyzed different trajectories like root mean square deviation (RMSD), a root mean square fluctuation (RMSF), hydrogen bonds (HBs) obtained from the MD simulation along with the change in binding free energy calculation using the AMBER18 (Agarwal et al, 2019;Al-Refaei et al, 2020;Cob-Calan et al, 2019;Nazarian et al, 2015;Pola et al, 2018).…”

“…RMSD trajectory is used to study structural stability of the protease with and without the compound as in Equation ( 2), while RMSF trajectory helps to investigate the flexibility in the presence or absence of compound (Cob-Calan et al, 2019). These values were calculated by using the following equations:…”

Lesson from Ecotoxicity: Revisiting the Microbial Lipopeptides for the Management of Emerging Diseases for Crop Protection

“…Moreover, several reports have already been initiated on the structure prediction and their possible interaction with different cellular protein/enzyme targets [207][208][209][210]. Cob-Calan et al [211] demonstrated the interactions of the cyclic lipopeptides iturin A, fengycin, and surfactin with β-tubulin using molecular docking and molecular dynamics simulation. A comparative study had shown that iturin A and fengycin had higher binding affinity as compared to surfactin for the catalytic site of β-tubulin [210,211].…”

“…Cob-Calan et al [211] demonstrated the interactions of the cyclic lipopeptides iturin A, fengycin, and surfactin with β-tubulin using molecular docking and molecular dynamics simulation. A comparative study had shown that iturin A and fengycin had higher binding affinity as compared to surfactin for the catalytic site of β-tubulin [210,211]. With the help of advancements in genetic engineering and synthetic biology, improved lipopeptide production with higher efficiency could be developed, targeting important pathosystems.…”