Exploring the molecular basis of the enantioselective binding of penicillin G acylase towards a series of 2-aryloxyalkanoic acids: A docking and molecular dynamics study

Lavecchia, Antonio; Cosconati, Sandro; Novellino, Ettore; Calleri, Enrica; Temporini, Caterina; Massolini, Gabriella; Carbonara, Giuseppe; Fracchiolla, Giuseppe; Loiodice, Fulvio

doi:10.1016/j.jmgm.2006.07.001

Cited by 21 publications

(7 citation statements)

References 56 publications

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“…For instance, the chiral recognition mechanism of PGA has been examined, by chromatography and other methods, for a series of 2-aryloxyacetic acids [166,167]. PGA has been immobilized to silica through amine or carboxylate groups and employed in an HPLC system for both hydrolyzing penicillin G and carrying out a chiral separation on the products [123].…”

Section: Chromatographic Studies Of Protein-based Cspsmentioning

confidence: 99%

Chromatographic Studies of Protein-Based Chiral Separations

Zheng

Azaria

et al. 2016

Separations

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The development of separation methods for the analysis and resolution of chiral drugs and solutes has been an area of ongoing interest in pharmaceutical research. The use of proteins as chiral binding agents in high-performance liquid chromatography (HPLC) has been an approach that has received particular attention in such work. This report provides an overview of proteins that have been used as binding agents to create chiral stationary phases (CSPs) and in the use of chromatographic methods to study these materials and protein-based chiral separations. The supports and methods that have been employed to prepare protein-based CSPs will also be discussed and compared. Specific types of CSPs that are considered include those that employ serum transport proteins (e.g., human serum albumin, bovine serum albumin, and alpha1-acid glycoprotein), enzymes (e.g., penicillin G acylase, cellobiohydrolases, and α-chymotrypsin) or other types of proteins (e.g., ovomucoid, antibodies, and avidin or streptavidin). The properties and applications for each type of protein and CSP will also be discussed in terms of their use in chromatography and chiral separations.

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Section: Chromatographic Studies Of Protein-based Cspsmentioning

confidence: 99%

Chromatographic Studies of Protein-Based Chiral Separations

Zheng

Azaria

et al. 2016

Separations

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show abstract

“…When predicting the posing of a ligand into a protein, docking can provide a good starting point for further calculations with the aim of evaluating the stability of the predicted interactions involved in binding [66]. In order to investigate the positional and conformational changes of inhibitors relative to the active pocket and reveal the binding stability, two 5 ns MD simulations were further performed based on the aforementioned docking complex structures considering the effects of the receptor flexibility and the explicit water solvation.…”

Section: Resultsmentioning

confidence: 99%

Combined 3D-QSAR, Molecular Docking and Molecular Dynamics Study on Derivatives of Peptide Epoxyketone and Tyropeptin-Boronic Acid as Inhibitors Against the β5 Subunit of Human 20S Proteasome

Liu

Zhang

Xiao

et al. 2011

IJMS

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An abnormal ubiquitin-proteasome is found in many human diseases, especially in cancer, and has received extensive attention as a promising therapeutic target in recent years. In this work, several in silico models have been built with two classes of proteasome inhibitors (PIs) by using 3D-QSAR, homology modeling, molecular docking and molecular dynamics (MD) simulations. The study resulted in two types of satisfactory 3D-QSAR models, i.e., the CoMFA model (Q2 = 0.462, R2pred = 0.820) for epoxyketone inhibitors (EPK) and the CoMSIA model (Q2 = 0.622, R2pred = 0.821) for tyropeptin-boronic acid derivatives (TBA). From the contour maps, some key structural factors responsible for the activity of these two series of PIs are revealed. For EPK inhibitors, the N-cap part should have higher electropositivity; a large substituent such as a benzene ring is favored at the C6-position. In terms of TBA inhibitors, hydrophobic substituents with a larger size anisole group are preferential at the C8-position; higher electropositive substituents like a naphthalene group at the C3-position can enhance the activity of the drug by providing hydrogen bond interaction with the protein target. Molecular docking disclosed that residues Thr60, Thr80, Gly106 and Ser189 play a pivotal role in maintaining the drug-target interactions, which are consistent with the contour maps. MD simulations further indicated that the binding modes of each conformation derived from docking is stable and in accord with the corresponding structure extracted from MD simulation overall. These results can offer useful theoretical references for designing more potent PIs.

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“…Furthermore, chiral recognition mechanism on PGA was investigated using molecular modeling and docking studies [29][30][31]. As depicted in Fig.…”

Section: Penicillin G-acylasementioning

confidence: 99%

Recent progresses in protein-based chiral stationary phases for enantioseparations in liquid chromatography

Haginaka

2008

Journal of Chromatography B

101

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Exploring the molecular basis of the enantioselective binding of penicillin G acylase towards a series of 2-aryloxyalkanoic acids: A docking and molecular dynamics study

Cited by 21 publications

References 56 publications

Chromatographic Studies of Protein-Based Chiral Separations

Chromatographic Studies of Protein-Based Chiral Separations

Combined 3D-QSAR, Molecular Docking and Molecular Dynamics Study on Derivatives of Peptide Epoxyketone and Tyropeptin-Boronic Acid as Inhibitors Against the β5 Subunit of Human 20S Proteasome

Recent progresses in protein-based chiral stationary phases for enantioseparations in liquid chromatography

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