Designing of phenol-based β−carbonic anhydrase1 inhibitors through QSAR, molecular docking, and MD simulation approach

Abstract

Tuberculosis (Tb) is an airborne infectious disease caused by () has emerged as one of the potential targets for new antitubercular drug development. In this work, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular docking, and molecular dynamics (MD) simulation approaches were performed on a series of natural and synthetic phenol-based inhibitors. The developed 3D-QSAR model ( = 0.94, = 0.86, and pred_r = 0.74) indicated that the steric and electrostatic factors are important parameters to modulate the bioactivity of phenolic compounds. Based on this indication, we designed 72 new phenolic inhibitors, out of which two compounds (D25 and D50) effectively stabilized receptor and, thus, are potential candidates for new generation antitubercular drug discovery program.

Screening Malaria-box compounds to identify potential inhibitors against SARS-CoV-2 Mpro, using molecular docking and dynamics simulation studies

“…The overall motion of the atoms in complexes was analysed for all the docked complexes, by plotting covariance matrices, to calculate the trace values with a maximum number of eigenvectors and amino acid residues. The matrix analysis also helped to understand the positional fluctuations on Cα-atoms and the atomic behaviour of the correlated and anti-correlated motions ( Ahamad et al, 2018 , 2019 bib_Ahamad_et_al_2018 bib_Ahamad_et_al_2019 ). The analysis is illustrated with two intense colour representations, red and blue.…”

“…The relative fluctuations of each amino acid were defined with Root Mean Square Fluctuations (RMSF). To measure the compactness of given molecule radius of gyrations (Rg) is implemented and the Solvent Accessible Surface Area (SASA) was employed to know the electrostatic contributions of molecular solvation ( Ahamad et al, 2018 , 2019 bib_Ahamad_et_al_2018 bib_Ahamad_et_al_2019 ; Kanipakam et al, 2020 ).…”

Insights into the structural and dynamical changes of spike glycoprotein mutations associated with SARS-CoV-2 host receptor binding

“…Finally, to make the system ready for production the fixing of constraints is achieved with the relaxation of the grid box with water along with the counterions. In the current study, all the simulations, including RBD WT and its six mutant structures; HR1 WT and its two mutant structures, were subjected to 100 ns simulations, each (Ahamad et al, 2018 , 2019 ).…”

“…The molecular motions in the systems- WT and mutant structures are examined with MD simulation, and the coordinates were saved at each interval from the obtained trajectories. The trajectory files were analyzed further to spot the positional deviations, relative fluctuations, direction of magnitude, change in atomic motions and hydrogen bond formations (Ahamad et al, 2018 , 2019 ; Kanipakam et al, 2020 ). The parameters were calculated for both WT (RBD & HR1) and mutant structures with different modules to identify the contributions of each atom in the protein that influences the structural stability and function of the prefusion SARS-CoV-2 spike glycoprotein.…”

“…formations (Ahamad et al, 2018(Ahamad et al, , 2019Kanipakam et al, 2020). The parameters were calculated for both WT (RBD & HR1) and mutant structures with different modules to identify the contributions of each atom in the protein that influences the structural stability and function of the prefusion SARS-CoV-2 spike glycoprotein.…”