Journal ArticleDOI
Molecular Dynamics Simulation and Binding Studies of β-Sitosterol with Human Serum Albumin and Its Biological Relevance
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TLDR
The molecular dynamics study makes an important contribution to understanding the effect of the binding of beta-sitosterol on conformational changes of HSA and the stability of a protein-drug complex system in aqueous solution.Abstract:
Beta-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 beta-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 beta-sitosterol through a static quenching mechanism. The binding constant of the compound to HSA, calculated from fluorescence data, was found to be K(beta-sitosterol) = 4.6 +/- 0.01 x 10(3) M(-1), which corresponds to -5.0 kcal M(-1) of free energy. Upon binding of beta-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 beta-sitosterol on conformational changes of HSA and the stability of a protein-drug complex system in aqueous solution. Molecular docking studies revealed that the beta-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 beta-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.read more
Citations
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Journal ArticleDOI
Structure, enzymatic activities, glycation and therapeutic potential of human serum albumin: A natural cargo
Gulam Rabbani,Sae-Young Ahn +1 more
TL;DR: Human serum albumin is one of the most suitable molecules for future research in drug discovery in pharmaceutical industry because of its numerous features and binding pattern that also governs the metabolism and drug dosage.
Journal ArticleDOI
Investigation of the interaction between amodiaquine and human serum albumin by fluorescence spectroscopy and molecular modeling
TL;DR: Both experimental results and modeling methods suggested that AQ binds mainly to the sub-domain IIA of HSA, and the efficiency of energy transfer and distance between HSA and acceptor AQ was calculated.
Journal ArticleDOI
Binding and molecular dynamics studies of 7-hydroxycoumarin derivatives with human serum albumin and its pharmacological importance.
Daniel Pushparaju Yeggoni,Mahesh Gokara,Darla Mark Manidhar,Aparna Rachamallu,Sailaja Nakka,Cirandur Suresh Reddy,Rajagopal Subramanyam +6 more
TL;DR: These studies revealed that 7-hydroxycoumarin derivatives caused an increased inhibition in growth of inflamed macrophages in a concentration-dependent manner with an IC50 of 78, 63, and 50 μM, suggesting that there are hydrophobic interactions when coumarin derivative-inspired drugs bind to HSA.
Journal ArticleDOI
Study on the interaction of the drug mesalamine with calf thymus DNA using molecular docking and spectroscopic techniques.
TL;DR: The results obtained from experimental and molecular modeling showed that 5-ASA is a minor groove binder of DNA and preferentially binds to GC rich regions.
Journal ArticleDOI
Study on the interaction of the epilepsy drug, zonisamide with human serum albumin (HSA) by spectroscopic and molecular docking techniques.
TL;DR: The results indicated that binding of ZNS to HSA caused strong fluorescence quenching of HSA through staticQuenching mechanism, hydrogen bonds and van der Waals contacts are the major forces in the stability of protein ZNS complex.
References
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Book ChapterDOI
Interaction Models for Water in Relation to Protein Hydration
TL;DR: In this article, a three-point charge model (on hydrogen and oxygen positions) with a Lennard-Jones 6-12 potential on the oxygen positions only was developed, and parameters for the model were determined from 12 molecular dynamics runs covering the two-dimensional parameter space of charge and oxygen repulsion.