Antimicrobial Peptide Designing and Optimization Employing Large-Scale Flexibility Analysis of Protein-Peptide Fragments

Abstract

The mankind relies on the use of antibiotics for a healthy life. The epidemic-like emergence of drug-resistant bacterial strains is increasingly becoming one of the leading causes of morbidity and mortality, which gives rise to design a potential antimicrobial peptide (AMP). Here, we have designed the potential AMP using the extensive dynamics simulation since protein–peptide interactions are linked to large conformational changes. Therefore, we have employed the advanced computational avenue CABS molecular docking method that enabled the flexible peptide-protein molecular docking with a large-scale rearrangement of the protein. Lead AMP was investigated against the wild-type (WT) and mutant-PBP5 (MT-PBP5) proteins (antiresistance property). AMP20 showed strong interactions with wtPBP5 and mtPBP5 and involvement of a large number of elements in interactions determined through an atomic model study. Full flexibility analysis showed the stable interaction of AMP20 with both the wild-type and mutant form of PBP5 with root-mean-square deviation (RMSD) values of ∼4.51 and 4.85 Å, respectively. Moreover, peptide dynamics showed involvement of all residues of AMP20 through contact map analysis, and extensive simulation confirmed the stable interaction of AMP20, with lower values of RMSD, radius of gyration, and root-mean-square fluctuation. This study paves the way for a potential approach to design the AMP with amino acid walking and large-scale conformational rearrangements of amino acids.

Cytotoxic T-lymphocyte elicited vaccine against SARS-CoV-2 employing immunoinformatics framework

“…Bridging the former evidences demanding specific CD8 + T cell responses in SARS-CoV-2 infections, the present study focuses primarily on the top-scoring CTL epitopes predicted using five different algorithms and subsequent identification of highly efficient common consensus epitopes. The use of molecular docking and molecular dynamics simulation assays assist in evaluating the potency and specificity of vaccine candidate with target receptors 27 . The designed vaccine construct was assessed for specific and robust binding with MHC receptors (MHC-1 and MHC-2) and virus-specific membrane receptor TLR-2 28 .…”

Accelerating the repurposing of FDA-approved drugs against coronavirus disease-19 (COVID-19)

“…17,18 Computational techniques are essential in these early stages of research as they can provide useful data in a short period, boosting the subsequent phases of research. [19][20][21][22][23][24][25] For instance, the accurate prediction of the binding affinity represents one of the most interesting eld of investigation. [26][27][28] Moreover, to date there is no vaccine available, and the computational repurposing campaigns are privileged approaches as they deal with already approved drugs that will not need to pass the entire pre-clinical phase.…”

Design and optimization of a subunit vaccine targeting COVID-19 molecular shreds using an immunoinformatics framework

“…56 We employed molecular docking and molecular dynamics simulation assays to evaluate the potency and specicity of the vaccine candidate with target receptors. 57,58 By using computational advancement avenues, we also performed an in silico immunization assay for the designed vaccine and assessed the strength of the vaccine construct to elicit the critical regulators of the immune system. Out of these signicant results, we propose the mechanism of action of the vaccine construct to evoke strong immune responses.…”