Computational docking of FtsZ: Survey of promising antibiotic compounds

Abstract

The bacterial cell-division protein FtsZ has been a promising antibiotic target for over a decade now, but there is still a need for more work in this area. So far there are no FtsZ targeting drugs commercially available. We have analyzed a wide variety of prospective drugs and their interactions with multiple FtsZ species using both free and directed docking simulations. Our goal is to present a standardized computational screening method for potential drug compounds targeting FtsZ. Our work is an example of a way to compare many proposed drugs and FtsZ species combinations relatively quickly. A common method for comparison can yield new results that individual studies and varying methods might not show, as we demonstrate here. To our knowledge this is one of the first, if not the first, computational docking study on the new E. coli FtsZ structures obtained in 2020.

Keywords: 0000; 1111; Antibiotics; FtsZ; Molecular docking.

Graphical abstract

Fig. 1

View of (A/C) 3wgn and (B/D) 6umk structures showing the H7 helix (red), the T7 loop (dark blue), the flexible loop containing amino acids 71-73 (purple), and the nucleotide binding site (orange) with nucleotide bound (surface representation). Panels C and D are rotated views of A and B, respectively. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

View of the free docking results for the nucleotide structures (positive controls). (A) 3wgn with GDP, (B) 6umk with GDP, (C) 3wgn with GTP, and (D) 6umk with GTP. The clusters are depicted as a composite of all docked results to illustrate that nearly all are found at the nucleotide binding site. The H7 helix is shown in red. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

View of (A) 3wgn and (B) 6umk docked with the drug compound Chrysophaentin A. The H7 helix is shown in red. The largest cluster is at the nucleotide binding site for both. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)