Binding interaction of a potential statin with β-lactoglobulin: An in silico approach

Baruah, Indrani; Borgohain, Gargi

doi:10.1016/j.jmgm.2021.108077

Cited by 9 publications

(9 citation statements)

References 42 publications

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“…The higher the fluctuating residues in the sequence, the more unstable the protein was 27 . The RMSF values of four key binding residues (Gly116, Trp82, Phe329 and His438) were further determined, as these residues were experimentally identified as stability indicators of BChE protein 28 . As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and biological evaluation of substituted acetamide derivatives as potential butyrylcholinestrase inhibitors

Yang

Liu

et al. 2023

Sci Rep

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Alzheimer’s disease (AD) is the most common type of age-related dementia. Inhibition of butyrylcholinesterase (BChE) emerge as an effective therapeutic target for AD. A series of new substituted acetamide derivatives were designed, synthesized and evaluated for their ability to inhibit BChE. The bioassay results revealed that several compounds displayed attractive inhibition against BChE). Among them, compound 8c exhibited the highest BChE inhibition with IC50 values of 3.94 μM. Lineweaver Burk plot indicated that 8c acted as a mixed-type BChE inhibitor. In addition, docking studies confirmed the results obtained through in vitro experiments, and showed that 8c bound to the catalytic anionic site (CAS) and peripheral anionic site (PAS) of BChE active site. Meanwhile, its ADME parameters were approximated using in silico method. Molecular dynamics simulation studies on the complex of 8c-BChE were performed, RMSD, RMSF, Rg, SASA, and the number of hydrogen bonds were calculated as well. These results implied that 8c could serve as appropriate lead molecule for the development of BChE inhibitor.

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Section: Resultsmentioning

confidence: 99%

Synthesis and biological evaluation of substituted acetamide derivatives as potential butyrylcholinestrase inhibitors

Yang

Liu

et al. 2023

Sci Rep

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“…Below, we outline recent contributions to modeling pH-dependent phenomena. It is well-understood that pH and conformational changes are coupled, and in recent times, many researchers have applied constant-pH MD (CpHMD) approaches to model the effect of pH on protein stability [ 24 ], binding [ 25 ], dynamics [ 82 ], and reactivity [ 83 ]. Additional complexity, if one investigates membrane proteins, comes from the presence of the lipid bilayer [ 84 ].…”

Section: Electrostatics Of Wild-type Biological Macromoleculesmentioning

confidence: 99%

“…Recent contributions to modeling pH-dependent phenomena are shown in Section 2.3 . Constant pH MD (CpHMD) approaches are an efficient tool to explore the effects of pH on biomolecular stability [ 24 ] and binding [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Electrostatics in Computational Biophysics and Its Implications for Disease Effects

Sun

Poudel

Alexov

et al. 2022

IJMS

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This review outlines the role of electrostatics in computational molecular biophysics and its implication in altering wild-type characteristics of biological macromolecules, and thus the contribution of electrostatics to disease mechanisms. The work is not intended to review existing computational approaches or to propose further developments. Instead, it summarizes the outcomes of relevant studies and provides a generalized classification of major mechanisms that involve electrostatic effects in both wild-type and mutant biological macromolecules. It emphasizes the complex role of electrostatics in molecular biophysics, such that the long range of electrostatic interactions causes them to dominate all other forces at distances larger than several Angstroms, while at the same time, the alteration of short-range wild-type electrostatic pairwise interactions can have pronounced effects as well. Because of this dual nature of electrostatic interactions, being dominant at long-range and being very specific at short-range, their implications for wild-type structure and function are quite pronounced. Therefore, any disruption of the complex electrostatic network of interactions may abolish wild-type functionality and could be the dominant factor contributing to pathogenicity. However, we also outline that due to the plasticity of biological macromolecules, the effect of amino acid mutation may be reduced, and thus a charge deletion or insertion may not necessarily be deleterious.

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“…BLG contains 162 amino acid residues and belongs to the family of lipocalins. Due to the presence of a hydrophobic calyx or core in its structure, BLG can accommodate many hydrophobic bioactive molecules and ensure the safe delivery of these molecules to their biological sites …”

Section: Introductionmentioning

confidence: 99%

“…Due to the presence of a hydrophobic calyx or core in its structure, BLG can accommodate many hydrophobic bioactive molecules and ensure the safe delivery of these molecules to their biological sites. 21 There are a multitude of research studies that have been dedicated to explore the interaction of the protein BLG with dietary polyphenols. Most of the studies revealed that the main essence of binding of BLG and polyphenols is through noncovalent interactions.…”

Section: Introductionmentioning

confidence: 99%

Insights into the Interaction between Polyphenols and β-Lactoglobulin through Molecular Docking, MD Simulation, and QM/MM Approaches

et al. 2022

Self Cite

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In this work, we have explored the interaction of three different polyphenols with the food protein β-lactoglobulin. Antioxidant activities of polyphenols are influenced by complexation with the protein. However, studies have shown that polyphenols after complexation with the protein can be more beneficial due to enhanced antioxidant activities. We have carried out molecular docking, molecular dynamics (MD) simulation, and quantum mechanics/molecular mechanics (QM/MM) studies on the three different protein–polyphenol complexes. We have found from molecular docking studies that apigenin binds in the internal cavity, luteolin binds at the mouth of the cavity, and eriodictyol binds outside the cavity of the protein. Docking studies have also provided binding free energy and inhibition constant values that showed that eriodictyol and apigenin exhibit better binding interactions with the protein than luteolin. For eriodictyol and luteolin, van der Waals, hydrophobic, and hydrogen bonding interactions are the main interacting forces, whereas for apigenin, hydrophobic and van der Waals interactions play major roles. We have calculated the root mean square deviation (RMSD), root mean square fluctuations (RMSF), solvent-accessible surface area (SASA), interaction energies, and hydrogen bonds of the protein–polyphenol complexes. Results show that the protein–eriodictyol complex is more stable than the other complexes. We have performed ONIOM calculations to study the antioxidant properties of the polyphenols. We have found that apigenin and luteolin act as better antioxidants than eriodictyol does on complexation with the protein, which is consistent with the results obtained from MD simulations.

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Binding interaction of a potential statin with β-lactoglobulin: An in silico approach

Cited by 9 publications

References 42 publications

Synthesis and biological evaluation of substituted acetamide derivatives as potential butyrylcholinestrase inhibitors

Synthesis and biological evaluation of substituted acetamide derivatives as potential butyrylcholinestrase inhibitors

Electrostatics in Computational Biophysics and Its Implications for Disease Effects

Insights into the Interaction between Polyphenols and β-Lactoglobulin through Molecular Docking, MD Simulation, and QM/MM Approaches

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