期刊
JOURNAL OF MOLECULAR LIQUIDS
卷 337, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.molliq.2021.116354
关键词
Cefoperazone; Albumin binding; Molecular docking; Molecular dynamics; Inner filter effect
资金
- Deanship of Scientific Research, King Saud University
- Applied Molecular Biosciences UnitUCIBIO - FCT/MCTES [UID/Multi/04378/2019]
- Fundacao para a Ciencia e a Tecnologia (FCT) Portugal [SFRH/BPD/97719/2013]
- Sharda University, India
The study investigated the binding of the cephalosporin-class drug cefoperazone with bovine serum albumin using spectroscopic techniques and in silico methods. The importance of correcting for the inner filter effect in this type of study was emphasized, and the binding mechanism was found to involve hydrogen bonding and hydrophobic forces with almost 1:1 static binding between BSA and CFP. Molecular docking and molecular dynamics simulation suggested the presence of a putative binding site between BSA domains 1 and 3, which could be a target for future research related to BSA-drug binding.
We investigated the binding of the cephalosporin-class drug cefoperazone (CFP) with bovine serum albumin (BSA) using spectroscopic techniques and in silico methods. The aim of this study was to (i) emphasize the importance of correcting for the inner filter effect in this type of study and (ii) understand the binding mechanism of CFP with BSA by addressing protein conformation and plausible binding sites. Formation of the complex was confirmed by UV-visible spectroscopy. Quenching of BSA fluorescence in the presence of CFP was also observed. Because of the high absorption of CFP in the fluorescence emission range of BSA, the fluorescence emission spectra were corrected for the inner filter effect. Fluorescence emission was studied at excitation wavelengths of 280 and 295 nm. The uncorrected data showed a significant contribution of tyrosine at the excitation wavelength of 280 nm; however, after correction, this contribution became negligible. The static-type mechanism was found to be involved in quenching, with almost 1:1 binding between BSA and CFP. Hydrogen bonding and hydrophobic forces were found to dominate the protein-ligand interactions with a slight decrease in the a-helical contents. Synchronous fluorescence spectral data (at Delta lambda = 15 and 60 nm) were also corrected for the inner filter effect, with the results being similar to those of excitation at 280 and 295 nm. Molecular docking and molecular dynamics (MD) simulation results suggest that, apart from the two known drug binding sites (drug site I and II), one putative binding site (binding site III) located between BSA domains 1 and 3 was also possible for CFP. MD simulations of the previously reported drug binding sites (drug site I and II) and putative binding site III revealed that binding site III showed excellent binding profiles and could be a target for future research related to BSA-drug binding. (C) 2021 Elsevier B.V. All rights reserved.
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