1st International and 10th National Iranian Conference on Bioinformatics
Home Accepted Papers
Experimental and Computational Studies of ND-Drived Schiff base ligands with HSA; Molecular Dynamics Simulation, QSAR Modeling and Molecular Docking Studies
Paper ID : 1437-ICB10
Authors:
Aria Tajally *1, Ahmad Amiri2, سودابه شکراللهی3
1دانشجوی کارشناسی ارشد شیمی معدنی دانشگاه تهران
2دانشکده علوم دانشگاه تهران
3شیمی دانشکده علوم دانشگاه تهران
Abstract:
Human Serum Albumin (HSA) is a negatively charged, is present in high concentration in plasma. Existence of several binding sites and an extraordinary binding capacity with a high degree of conformational flexibility makes HSA a versatile carrier to transport a variety of endogenous and exogenous ligands including drug molecule [1]. Herein, twelve Schiff-base ligands (L1-L12) have been synthesised by the reaction of 1,5-naphthalenediamine (ND) with four aldehyde drivatives and characterised by different spectroscopic techniques. The interaction of these ligands with HSA was investigated under pseudo-physiological conditions by fluorescence and circular dichroism (CD). The fluorescence quenching of HSA at 343 nm upon addition of the L1-L12, reveals the formation of complexes between Schiff-bases and HSA. The magnitude of the Kq values for L1-L12 ligands (greater than 2.0 × 1010 M−1 s−1) confirm the static mechanism for quenching. Furthermore, the CD spectra show that the random coil and antiparallel parts of the secondary structure have trends inverse to the helix part in the presence of Schiff base ligands. The optimization of the structures was performed by using DFT/B3LYP method with the 6–311++G(d,p) basis set [2]. Finally, the molecular docking studies with AutoDocVina software and molecular dynamics simulations using Gromacs package were applied to estimate the binding affinity between HSA and L1-L12 ligands. The results show the strong intreraction between the protein and the ligands with the binding affinities in the range of -7.2 ─ -11.1 kcal/mol. The diffrences of the binding constants for the interaction of L1-L12 with HSA was realized by QSAR toolbox.
Keywords:
Schiff Base; HSA Binding; Molecular Docking; DFT; Circular Dichroism; MTT assay, Gromacs package, Qaussian,Q-SAR toolbox.
Status : Paper Accepted (Poster Presentation)