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

FERRARI, I. V.; Patrizio, P.

2021-07-10 bioinformatics
10.1101/2021.07.09.451789 bioRxiv
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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.

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