Biology subjects

FERRARI, I. V.

Publications and source records attributed to FERRARI, I. V..

4 recordsLinked to original sources

bioRxiv2021

Docking Molecular analysis of potential Aldosterone antagonists

BackgroundAldosterone antagonists (spironolactone, eplerenone) inhibit the action of aldosterone in the collecting duct; as such, these agents cause modest diuresis but inhibit potassium and hydrogen ion secretion. We report first time Potential Aldosterone antagonists by in Silico approach, using AutoDock Vina and AutoDock 4 (or MGL Tool), estimated with Pyrx and AM Dock Software, calculating three different important parameters: Binding Affinity (kcal/mol), estimated Ki (in nM units) and Ligand Efficiency (L.E. in kcal/mol). After a selective analysis of over 1000 drugs, processed with Pyrx (a Virtual Screening software for Computational Drug Discovery) in the Ligand Binding site pocket of the protein (ID PDB 2OAX Chain A:), we noticed high values of Binding Energy, about -13.55 kcal/mol estimated by AutoDock 4 with AM Dock Software, concluding that it could be an excellent candidate drug, compared to everyone else Aldosterone antagonists. Indeed, from the results of AutoDock Vina and AutoDock 4 (or AutoDock 4.2), implemented with Lamarckian genetic algorithm, LGA, trough AMDock Software, our results of Binding Energy are very similar to the crystallized Spironolactone in PDB 2OAX Chain A protein.

bioinformatics↗

bioRxiv2021

Docking Molecular analysis of potential Drug Paritaprevir against Mycobacterium tuberculosis (Mtb)

BackgroundMycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, which kills 1.8 million annually. This is an infectious disease generally affects the lungs, but can also affect other parts of the body. Mtb RNA polymerase (RNAP) is the target of the first-line antituberculosis drug Rifampin (Rif). We report first time a Potential Drug Paritaprevir against with severe infectious disease, by in Silico approach, using Autodock Vina and Autodock 4 (or MGL Tool), estimated with Pyrx and AMDock Software, calculating three different important parameters: Binding Affinity (kcal/mol), estimated Ki (in nM units) and Ligand Efficiency (L.E. in kcal/mol). After a selective analysis of over 1000 drugs, processed with Pyrx (a Virtual Screening software for Computational Drug Discovery) in the Ligand Binding site pocket of the protein (ID PDB 5UHB chain C,DNA-directed RNA polymerase subunit beta), we noticed high values of these 3 parameters mentioned above of Paritaprevir, concluding that it could be an excellent candidate drug for this type of infection. Indeed, from the results of Autodock Vina and Autodock 4 (or Autodock 4.2), implemented with lamarckian genetic algorithm, LGA, trough AMDock Software, This oral drug, approved by FDA in 2014, both by Autodock Vina and Autodock Vina 4 has excellent Binding affinity value, ca. -10.00 kcal/mol, a Ki value 40 nM and Ligand efficiency ca -0.15 kcal/mol. These results are comparable to the drug crystallized in the above-mentioned protein, currently used against TBC.

bioinformatics↗

bioRxiv2021

Study of Basic Local Alignment Search Tool (BLAST) and Multiple Sequence Alignment (Clustal- X) of Monoclonal mice/human antibodies

In this work, we have focused on the study of the Basic Local Alignment Search Tool (BLAST) and Multiple Sequence Alignment (Clustal-X) of different monoclonal mice antibodies to understand better the multiple alignments of sequences. Our strategy was to compare the light chains of multiple monoclonal antibodies to each other, calculating their identity percentage and in which amino acid portion. (See below figure 2) Subsequently, the same survey of heavy chains was carried out with the same methodology. (See below figure 3) Finally, sequence alignment between the light chain of one antibody and the heavy chain of another antibody was studied to understand what happens if chains are exchanged between antibodies. (See below figure 4) From our results of BLAST estimation alignment, we have reported that the Light Chains (Ls) of Monoclonal Antibodies in Comparison have a sequence Homology of about 60-80% and they have a part identical in sequence zone in range 100-210 residues amino acids, except ID PDB 4ISV, which it turns out to have a 40% lower homology than the others antibodies. As far as, the heavy chains (Hs) of Monoclonal Antibodies are concerned, however they tend to have a less homology of sequences, compared to lights chains consideration, equal to 60%-70% and they have an identical part in the sequence zone between 150-210 residues amino acids; with the exception of ID PDB 3I9G-3W9D antibodies that have an equal homology at 50%. (See supporting part) Summing up: about 70-80% identity among 2 light chains of 2 antibodies, 60-70% identity between 2 heavy chains of 2 antibodies, 30% identity between the two chains of a antibody and 30% if you compare the light chain of one antibody with the heavy chain of another antibody. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=190 SRC="FIGDIR/small/451785v2_fig2.gif" ALT="Figure 2"> View larger version (61K): org.highwire.dtl.DTLVardef@1a5d6b1org.highwire.dtl.DTLVardef@b214daorg.highwire.dtl.DTLVardef@176fed3org.highwire.dtl.DTLVardef@153eb17_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFig 2C_FLOATNO Comparison of two light chains between 5 antibodies C_FIG O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=190 SRC="FIGDIR/small/451785v2_fig3.gif" ALT="Figure 3"> View larger version (57K): org.highwire.dtl.DTLVardef@6f66f9org.highwire.dtl.DTLVardef@1d19afforg.highwire.dtl.DTLVardef@17119forg.highwire.dtl.DTLVardef@85fe98_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFig 3C_FLOATNO Comparison of two heavy chains between 5 antibodies C_FIG O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=130 SRC="FIGDIR/small/451785v2_fig4.gif" ALT="Figure 4"> View larger version (43K): org.highwire.dtl.DTLVardef@10dc2f7org.highwire.dtl.DTLVardef@7b0885org.highwire.dtl.DTLVardef@16c72c8org.highwire.dtl.DTLVardef@e3c1d1_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFig 4C_FLOATNO Comparison of two light chains (ID PDB 1PSK and ID PDB 1F11) of antibodies, estimated on the left side by ClustalX and on the right side by BLAST C_FIG

bioinformatics↗

bioRxiv2021

Development and Validation Molecular Docking Analysis of Human serum albumin (HSA)

BackgroundHAS (Human Serum Albumin) is a highly water-soluble globular plasma protein, with a relative molecular weight (g/mol) of 67 KDa, consisting of 585 amino acid residues. In this study, we have investigated the interaction of the Crystal structures complexed in human serum albumin at resolutions of 2.8 to 2.0: Camptothecin, 9-amino-camptothecin, Etoposide, Teniposide, Bicalutamide and Idarubicin, using a bioinformatic approach, estimated by Pyrx Virtual Screen Tool and AMDock (AMDock, Assisted Molecular Docking). We have analyzed a validated protocol, studying several parameters, as Binding Affinity, RMSD value, Ligand Efficiency, and Inhibition constant (Ki value). MethodsHuman Serum Albumin protein preparation was characterized with several programs, as Chimera, MGLTools 1.5.6, Swiss PDB Viewer Software to perform docking analysis by Autodock Vina estimated with Pyrx Software. ResultsIn this work, we have found crystalized camptothecin, crystalized 9-amino-camptothecin and crystalized teniposide, gave excellent results for Binding Affinity, (kcal/mol), RMSD value (A{degrees}), inhibition constant Ki value (nM): -Binding Affinity of 9-amino-camptothecin (ca.-10 kcal/mol), camptothecin (-9 kcal/mol) and teniposide (-11 kcal/mol, -RMSD Value of 9 -amino-camptothecin (ca.1.8 [A]), camptothecin (ca.2.2 [A]) and teniposide (ca. 3.6 [A]), - Ki Value: 9 -amino-camptothecin (ca 59 nM), camptothecin (ca 183 nM) and teniposide (ca 9 nM), -Ligand efficiency: of 9 -amino-camptothecin(ca -0.35 kcal/mol), camptothecin (ca -0.34 kcal/mol) and teniposide (ca -0.24 kcal/mol ConclusionsWe explored the best three crystallized ligand in Human Serum Albumin. Moreover, we observe a complete overlap, during the re-docking analysis phase, estimated by chimera Software. Therefore we have concluded that ID PDB Crystal 4L8U human serum albumin-Crystallised 9 -amino Camptothecin; ID PDB Crystal 4L9K human serum albumin-Crystallised Camptothecin and ID PDB Crystal 4L9Q human serum albumin-crystallized teniposide be used as a possible as a reference template protein to be compared with the target protein, by Docking molecular analysis.

bioinformatics↗