A computational quest for identifying potential vaccine candidates against <i>Moraxella lacunata</i>: a multi-pronged approach
Creators: name: Ullah, Asad
name: Haq, Mahboob ul
name: Iqbal, Madiha
name: Irfan, Muhammad
name: Khan, Saifullah
name: Muhammad, Riaz
name: Ullah, Amin
name: Khurram, Muhammad
name: Alharbi, Metab
name: Alasmari, Abdullah F.
name: Ahmad, Sajjad
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biophysics
subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: Cell Biology
subject: Genetics
subject: Molecular Biology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences

description: <i>Moraxella lacunata</i> is an emerging gram-negative bacterium that is responsible for multiple nosocomial infections. The bacterium is evolving resistance to several antibiotics, and currently, no effective licensed vaccines are available, which warrants the search for new therapeutics. A multi-epitope-based vaccine has been designed for <i>M. lacunata</i>. The complete proteome of <i>M. lacunata</i> contains 10,110 core proteins. Subcellular localization analysis revealed the presence of five proteins in the extracellular matrix, while 19 proteins were predicted to be located in the outer membrane, and 21 proteins were predicted to be located in the periplasmic region. Only two proteins, the type VI secretion system tube protein (Hcp) and the transporter substrate-binding domain-containing protein, were selected for epitope prediction as they fulfilled all the criteria for being potential vaccine candidates. Shortlisted epitopes from the selected proteins were fused together using “GPGPG” linkers to overcome the limitations of single-epitope vaccines. Next, the cholera toxin-B adjuvant was attached to the peptide epitope using an EAAAK linker. Docking analysis was performed to examine the interaction between the vaccine and immune cell receptors, revealing robust intermolecular interactions and a stable binding conformation. Molecular dynamics simulation findings revealed no drastic changes in the binding conformation of complexes during the simulation period. The net binding free energy of vaccine-receptor complexes was estimated using the molecular mechanics energies combined with the Poisson–Boltzmann and surface area continuum solvation (MM-PBSA) method. The reported values were −586.38 kcal/mol, −283.74 kcal/mol, and −296.88 kcal/mol for the TLR-4-vaccine complex, MHC-I-vaccine complex, and MHC-II-vaccine complex, respectively. Furthermore, the molecular mechanics energies combined with the generalized Born and surface area continuum solvation (MM-GBSA) analysis predicted binding free energies of −596.69 kcal/mol, −287.39 kcal/mol, and −298.28 kcal/mol for the TLR-4-vaccine complex, MHC-I-vaccine complex, and MHC-II-vaccine complex, respectively. The theoretical vaccine design proposed in the study could potentially serve as a powerful therapeutic against targeted pathogens, subject to validation through experimental studies. Communicated by Ramaswamy H. Sarma