A computational structural biology study to understand the impact of mutation on structure–function relationship of inward-rectifier potassium ion channel Kir6.2 in human

In-silico approaches to detect inhibitors of the human severe acute respiratory syndrome coronavirus envelope protein ion channel

“…To gain detail insight into the structural characteristic of the downloaded protein and removing any conflicts present between its atoms of main and side chain Gouda et al, 2020;Gupta & Vadde, 2020b), MDS were employed using 'Gromos96-43a1 force field' of 'GROMACS 5.1' for 200 ns (Abraham et al, 2015). As 'SARS-CoV2 E' protein resides is a transmembrane region, at first, downloaded structure of 5 Â 29 was embedded in the 'equilibrated bilayer of DPPC (dipalmitoylphosphatidylcholine)' using 'g_membed' tool of 'GROMACS 5.1' (Wolf et al, 2010) using the aid of 'Berger lipids' derived parameters from 'Berger, Edholm, and Jahnig' (Berger et al, 1997).…”

“…Further solvation of the entire system till energy minimization followed by equilibrating the complete system under NVT ('Constant Number of Particles, Pressure and Temperature') and NPT ('Constant Number of Particles, Volume, and Temperature') conditions were carried out as stated in detail at http://www.mdtutorials.com/gmx/ membrane_protein/index.html. Final molecular dynamic (MD) trajectories as well as the quality of simulations were analyzed via 'GROMACS 5.1' (Gupta & Vadde, 2020b). 'Principal Component Analysis' (PCA) was also carried out for capturing the most flexible area and the motion of the a-helix & the b-strands present within the protein during 200 ns.…”

“…'Principal Component Analysis' (PCA) was also carried out for capturing the most flexible area and the motion of the a-helix & the b-strands present within the protein during 200 ns. Equilibrated conformers from the MD were used to produce the mean structure of the 'SARS-CoV2 E' protein (Gupta & Vadde, 2020b). Backbone atoms' free energy for the 'SARS-CoV2 E' protein was calculated using the 'GROMACS 5.1' from 20 ns to 200 ns with 20 ns interval (Gupta & Vadde, 2020b).…”

“…The active site pocket present in the 'SARS-CoV2 E' protein was calculated using the CASTp server (Binkowski et al, 2003). Active pocket with the highest volume as well as area was considered for molecular docking studies with phytochemicals having 250 conformations Gupta & Vadde, 2020b) via the AutoDock (Morris et al, 2009) tool. Three best phytochemical having the minimal binding energy was considered for further study (Gupta & Vadde, 2020b).…”

“…For gaining detail insight into the structure & function, to date numerous 'three-dimensional' structures of the 'SARS-CoV E' protein have been deposited in the 'Protein Data Bank (PDB)'. Furthermore, as identifying novel drugs through laboratory approaches demands huge capital as well as investments, there is a continuous demand for screening drug molecules via high screeening computational methods that saves both money as well as times Gupta & Vadde, 2020b;Gupta & Vadde, 2020a). Nevertheless, ADMET ('Absorption, Distribution, Metabolism, Excretion and Toxicity') as well as 'Lipinski's Rule of 5s' property passed natural drugs may have either minimum or no adverse-effects Gupta & Vadde, 2020a,b).…”