Molecular docking analysis of long-chain alkanes with the β-lactamase BEL-1 from P. aeruginosa

Pseudomonas aeruginosa is a gram-negative opportunistic bacterium that is a concern worldwide due to its innate antibiotic resistance properties. This warrants the development of non-antibiotic compounds that can potentially address the growing concern. Therefore, it is of interest to document the molecular docking analysis data of three long-chain alkanes, namely, eicosane, triacontane, and nonadecane with β-lactamase BEL-1. Data shows that nonadecane have good binding features and drug-likeness when compared to triacontane and nonadecane. It is well known that nonadecane is a compound that is abundantly available from natural resources for further consideration.


Background:
Pseudomonas aeruginosa is an opportunistic gram-negative bacterium that can be seen along with nosocomial infections [1]. The genome sequence of P. aeruginosa is relatively large   [2]. They are resistant to external stress, colonise easily, and rapidly develop a matrix of biofilm. P. aeruginosa consists of resistance-nodulation division efflux pumps which protect against antibiotics [3,4]. The biofilm formed also provides resistance to antibiotics. P. aeruginosa strains have multiple drug-resistant [5]. A clinical strain of P. aeruginosa consisting of clavulanic acid-inhibited ambler class A extended-spectrum β-lactamase (BEL-1) was reported [6,7]. BEL-1 is chromosomally encoded in class 1 integrons and has an association with cephalosporinase and penicillinase and it shows resistance against β-lactam antibiotics, including carbapenems [6,8]. The development of BEL-1 strain containing P. aeruginosa is a concern amidst the growing multi drug resistance bacterial species. Besides, the BEL-1 strain containing P. aeruginosa have low MIC and is sparsely detectable with conventional methods [9]. The World Health Organisation listed carbapenem resistant P. aeruginosa as a bacterial species that requires the development of a novel class of antibiotics for treatment [10]. New class of antibiotics will become vulnerable to the antibiotic resistance properties of the bacterium [11]. Non-antibiotic compounds with features such as inhibition of quorum sensing and bacterial lectins, phage therapy, vaccines, nanoparticles, etc are known [12,13]. There are several research groups working on developing novel therapies from naturally available resources such as fungi, plants, etc [14 -17]. Therefore, it is of interest to document the molecular docking analysis data of plant derived three long-chain alkanes, namely, eicosane, triacontane, and nonadecane with β-lactamase BEL-1.

Materials and Methods: Protein preparation:
Molecular structure reported at the Protein Data Bank (PDB) was retrieved for extended-spectrum β-lactamase BEL-1 (PDB ID: 5EUA). The structure was energy minimised and converted to PDBQT format.

Ligand preparation:
The compounds eicosane, triacontane, and nonadecane were selected as ligands for docking and their 3D structures were taken from PubChem. It was then minimized by applying Gasteiger and Kollman's charge. The root of the structure was detected, torsion was applied, and the structures were saved in PDBQT and Mol2 format.

Molecular Docking and binding profile:
Molecular docking analyses were carried out using PyRx -Python Prescription 0.8. The compounds were targeted to the protein with a grid-box docking model to determine the binding energies. Furthermore, the interaction between the amino acids and compounds was identified using Cresset Flare 4.0.1. Besides, clogP, PSA, TSA, TPSA, drug-likeness, etc., were determined using Osiris Data warrior 5.5.0.  Data shows that the compounds have considerable binding features with the antibiotic resistance β-lactamase BEL-1 from P. aeruginosa, with a drug-likeness value of -23.454 for nonadecane and -20.398 for both eicosane and triacontane. Moreover, the compounds did not have any mutagenic or tumorigenic activity. The compounds also obey Lipinski's rule of five. Eicosane, triacontane, and nonadecane are long-chain alkanes found in essential oils. . Therefore, it is of interest to document the molecular docking analysis data of three long-chain alkanes, namely, eicosane, triacontane, and nonadecane with βlactamase BEL-1. Data shows that nonadecane have good binding features and drug-likeness when compared to triacontane and nonadecane. I

Conclusion:
M. acumanata flower is commonly consumed in India. It has several medicinal properties. Studies show potential antibacterial and anticancer activities from this flow. Hence, we document the molecular docking analysis data of long-chain alkaneseicosane, triacontane, and nonadecane, with the BEL-1 of P. aeruginosa for further consideration with nonadecane shows optimal binding. Nonadecane is abundantly available and can be developed as potential non-antibiotic therapeutics to treat antibacterial infections, especially P. aeruginosa.

Source of Funding:
No funding was received for this study.