Department of Plant Sciences
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Browsing Department of Plant Sciences by Author "Ahalawat, Navjeet"
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ItemMolecular dynamics simulation and binding studies of β-sitosterol with human serum albumin and its biological relevance( 2010-07-15) Sudhamalla, Babu ; Gokara, Mahesh ; Ahalawat, Navjeet ; Amooru, Damu G. ; Subramanyam, Rajagopalβ-Sitosterol is a naturally occurring phytosterol that is widely used to cure atherosclerosis, diabetes, cancer, and inflammation and is also an antioxidant. Here, we studied the interaction of β-sitosterol, isolated from the aerial roots of Ficus bengalensis, with human serum albumin (HSA) at physiological pH 7.2 by using fluorescence, circular dichroism (CD), molecular docking, and molecular dynamics simulation methods. The experimental results show that the intrinsic fluorescence of HSA is quenched by addition of β-sitosterol through a static quenching mechanism. The binding constant of the compound to HSA, calculated from fluorescence data, was found to be K β-sitosterol = 4.6 ± 0.01 - 103 M -1, which corresponds to -5.0 kcal M-1 of free energy. Upon binding of β-sitosterol to HSA, the protein secondary structure was partially unfolded. Specifically, the molecular dynamics study makes an important contribution to understanding the effect of the binding of β-sitosterol on conformational changes of HSA and the stability of a protein-drug complex system in aqueous solution. Molecular docking studies revealed that the β-sitosterol can bind in the large hydrophobic cavity of subdomain IIA, mainly by the hydrophobic interaction but also by hydrogen bond interactions between the hydroxyl (OH) group of carbon-3 of β-sitosterol to Arg(257), Ser(287), and Ala(261) of HSA, with hydrogen bond distances of 1.9, 2.4, and 2.2 A, respectively. © 2010 American Chemical Society.
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ItemMolecular dynamics simulation studies of betulinic acid with human serum albumin( 2012-06-01) Malleda, Chandramouli ; Ahalawat, Navjeet ; Gokara, Mahesh ; Subramanyam, RajagopalBetulinic acid (BA) is a naturally occurring pentacyclictriterpenoid possessing anti-retroviral, anticancer, and anti-inflammatory properties. Here, we studied the interaction of BA with human serum albumin (HSA) by using molecular docking, and molecular dynamic simulation methods. Molecular docking studies revealed that BA can bind in the large hydrophobic cavity of drug binding site I of sub-domain IIA and IIB, mainly by the hydrophobic interactions and also by hydrogen bond interactions. In which several cyclohexyl groups of BA are interacting with Phe (206), Arg(209), Ala(210), Ala(213), Leu(327), Gly(328), Leu(331), Ala(350), and Lys(351), residues of sub-domain IIA and IIB of HSA by hydrophobic interactions. Also, hydrogen bond interactions were observed between the hydroxyl (OH) group of BA with Phe(206) and Glu(354) of HSA, with hydrogen bond distances of 0.24 nm,0.28 nm respectively. Further, specifically, the molecular dynamics study makes an important contribution in understanding the effect of the binding of BA on conformational changes of HSA and the stability of the protein-drug complex system in aqueous solution. The root mean square deviation values of atoms in the free HSA molecule were calculated from 3000 ps to 5000 ps trajectory and the results were obtained as 0.72± 0.036 nm and 0.81±0.032 nm for free HSA and HSA-BA, respectively. The radius of gyration (Rg) values of both unliganded HSA and HSA-BA were stabilized at 2.59± 0.03 nm, 2.51±0.01 nm, respectively. Thus, this work may play an important role in the design of new BA inspired drugs with desired HSA binding affinity. © Springer-Verlag 2011.