Combined docking, molecular dynamics simulations and spectroscopic studies for the rational design of a dipeptide ligand for affinity chromatography separation of human serum albumin

Aghaee, Elham; Ghasemi, Jahan B.; Manouchehri, Firouzeh; Balalaie, Saeed

doi:10.1007/s00894-014-2446-7

Cited by 41 publications

(16 citation statements)

References 67 publications

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“…Of note, in the HSA titration of CHAP, the heat included a negative value. HSA molecules contain a hydrophobic pocket that can be combined with the hydrophobic center of the NP [ 43 ], so the interaction triggered by the first four drops of HSA and CHAP are primarily driven by hydrophobic forces. Although HSA is negatively charged and CHAP is positively charged, starting from the fifth drop, there is also a charge force between HSA and CHAP because of the endothermic nature of the reaction.…”

Section: Resultsmentioning

confidence: 99%

Pullulan-Based Nanoparticle-HSA Complex Formation and Drug Release Influenced by Surface Charge

et al. 2018

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The nanomaterial composition of nanoparticles and their protein adsorption in the blood is of great significance in the design of drug-loaded nanoparticles. To explore the interaction between the different surface components of nanoparticles (NPs) and protein, we synthesized three kinds of pullulan NP polymers: cholesteric hydrophobically (CH) modified pullulan (CHP), CH-modified animated pullulan (CHAP), and CH-modified carboxylated pullulan (CHSP). Pullulan NPs were prepared by the dialysis method. Dynamic light scattering was used to determine the charge and size of the three NPs. The size of NPs was altered by the number of charge groups when polymers contain the same degree of cholesterol substitution. The zeta potentials were + 12.9, − 15.4, and − 0.698 mV for CHAP, CHSP, and CHP, respectively, and the dimensions were 116.9, 156.9, and 73.1 nm, respectively. Isothermal titration calorimetry was used to determine the thermodynamic changes of NPs with different surface charge, and the effect of human serum albumin (HSA) on the titration was investigated. The changes of enthalpy and entropy demonstrated an interaction between NPs and HSA; the binding constant (Kb) for CHSP, CHP, and CHAP was 1.41, 27.7, and 412 × 104 M−1, respectively, with the positive charge for CHAP–HSA, uncharged for CHP–HSA, and negative charge for CHSP–HSA complex. Fluorescence and circular dichroism spectroscopy were used to determine the protein structure change after the complexation between NPs and HSA. The NP and HSA complexation is a complicated process composed of protein α-helical content reduction and the peptide chain extension; CHP NPs had the largest reduction in HSA α-helical content. The drug release rates of all compounds of NP and HSA were significantly lower than those of free drug and drug-loaded NPs after 48 h. The highest and lowest rates were observed in CHSP–HSA and CHP–HSA, respectively. The drug release was significantly influenced by the adsorption of HSA on NPs, and the size and surface charge of NPs played an important role in this process.

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Section: Resultsmentioning

confidence: 99%

Pullulan-Based Nanoparticle-HSA Complex Formation and Drug Release Influenced by Surface Charge

et al. 2018

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“…During the preparation phase, the minimization and equilibration of constrained complexes were performed in a 15 Å3-sized water box [ 41 ], and an Amber12 EHT force field file was applied for energy minimization and equilibration with Gasteiger-Huckel charges using Boltzmann initial velocity. Restrictive MD simulations were carried out after the preparation phase, while gradually raising the system temperature from 300 to 310 K, and maintaining pressure at 101.325 kPa within 100 ps [ 42 , 43 ]. Finally, a 5 ns MD non-restrictive MD simulation with a 2 fs timestep, was carried out to investigate the stability and affinity of the ligand-receptor complex by contrasting the root mean square deviations (RMSD) [ 41 , 43 ].…”

Section: Methodsmentioning

confidence: 99%

Study of Imidazolium Salt Derivatives as PIK3CA Inhibitors Using a Comprehensive in Silico Method

Wang

Liang

et al. 2018

IJMS

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A series of imidazolium salt derivatives have demonstrated potent antitumor activity in prior research. A comprehensive in silicon method was carried out to identify the putative protein target and detailed structure-activity relationship of the compounds. The Topomer CoMFA and CoMSIA techniques were implemented during the investigation to obtain the relationship between the properties of the substituent group and the contour map of around 77 compounds; the Topomer CoMFA and CoMSIA models were reliable with the statistical data. The protein-protein interaction network was constructed by combining the Pharmmapper platform and STRING database. After generating the sub-network, the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA with protein data bank ID: 3ZIM) was selected as the putative target of imidazolium salt derivatives. A docking study was carried out to correlate interactions of amino acids in protein active pockets surrounded by the ligand with contour maps generated by the structure-activity relationship method. Then the molecular dynamics simulations demonstrated that the imidazolium salt derivatives have potent binding capacity and stability to receptor 3ZIM, and the two ligand-receptor complex was stable in the last 2 ns. Finally, the ligand-based structure-activity relationship and receptor-based docking were combined together to identify the structural requirement of the imidazolium salt derivatives, which will be used to design and synthesize the novel PIK3CA inhibitors.

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“…However, the direct grafting of ligands to matrix will restrict the large‐scale application of the resins. Fortunately, polymer as spacer arm could improve ligand spatial distribution and ligand density to the grafted resin [13,14].…”

Section: Introductionmentioning

confidence: 99%

A novel dextran‐grafted tetrapeptide resin for antibody purification

Fang

Zhu

Lin

et al. 2020

J of Separation Science

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Short peptide biomimetic affinity chromatography as a novel antibody separation chromatography is a potential alternative to protein A chromatography. However, if directly attaching ligand to matrix, the adsorption capacity and mass transfer rate would be affected by pore blockage and steric effect. Grafting resin is an effective method to solve this problem by using polymer as a bridge between matrix and ligand. In this work, a novel resin was prepared by grafting a tetrapeptide to the dextran-grafted matrix. Then, the adsorption properties for human immunoglobin G and BSA were determined. The results showed the saturation adsorption capacity could reach to 133 mg/g resin at pH 8.9 with a significantly low dissociation constant (0.03 mg/mL). The influence of flow rates to dynamic binding capacity of this resin was less than that of the non-grafted resin. The separation performance of the resin showed monoclonal antibody could be well isolated from the Chinese hamster ovary culture supernatant at pH 9.0 with the purity of 93.0% and yield of 84.7% by one step. Overall, this resin could achieve higher binding capacity by the possible of gaining higher ligand density, indicating its potential significance for separation in larger scale systems.

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Combined docking, molecular dynamics simulations and spectroscopic studies for the rational design of a dipeptide ligand for affinity chromatography separation of human serum albumin

Cited by 41 publications

References 67 publications

Pullulan-Based Nanoparticle-HSA Complex Formation and Drug Release Influenced by Surface Charge

Pullulan-Based Nanoparticle-HSA Complex Formation and Drug Release Influenced by Surface Charge

Study of Imidazolium Salt Derivatives as PIK3CA Inhibitors Using a Comprehensive in Silico Method

A novel dextran‐grafted tetrapeptide resin for antibody purification

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