Molecular insight into protein binding orientations and interaction modes on hydrophobic charge-induction resin

Tong, Hong-Fei; Cavallotti, Carlo; Yao, Shan-Jing; Lin, Dong‐Qiang

doi:10.1016/j.chroma.2017.06.071

Cited by 16 publications

(7 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Herein, the molecular interaction between GPcl and ADI-15946 was studied using molecular dynamics (MD) simulation and MM–PBSA method (molecular mechanics–Poisson–Boltzmann surface area), for the biomimetic design of neutralizers against EBOV based on the structure of ADI-15946. MD simulation − in combination with MM–PBSA (molecular mechanics–Poisson–Boltzmann surface area) analysis has been widely used to investigate the interface behavior of protein molecules, especially with the advantages of a quantitative assessment of the relative contribution of each residue in the binding process. Herein, the molecular details on the binding of ADI-15946 on GPcl were studied for the biomimetic design of neutralizer, using a crystal structure of GPcl and ADI-15946 determined recently as the template.…”

Section: Introductionmentioning

confidence: 99%

Biomimetic Design of Peptide Neutralizer of Ebola Virus with Molecular Simulation

Hou

Zhang

2020

Langmuir

View full text Add to dashboard Cite

Ebola virus (EBOV) belongs to the Filoviridae family, which can cause severe hemorrhagic fever in humans and nonprimates. The neutralization of EBOV by monoclonal antibody (mAb) ADI-15946 was reported recently. In the present study, the molecular interactions between the receptor GPcl of EBOV and ADI-15946 were studied by molecular dynamics (MD) simulation and molecular mechanics–Poisson–Boltzmann surface area (MM–PBSA) analysis. Hydrophobic interaction was identified as the main driving force for the binding of ADI-15946 on EBOV. Moreover, the contribution of each amino acid residue for the binding was evaluated. Then, an affinity binding model (ABM) was constructed using the residues favorable for the binding, including Y107, F108, D109, W110, and R113. The biomimetic design of neutralizer against EBOV according to the ABM of ADI-15946 was then performed, followed by screening using docking, structural similarity. Two neutralizers YFDWHMR and YFDWRYR were obtained, which were proven to be capable of strong binding on GPcl and then neutralizing GPcl. These results would be helpful for the development of neutralizers for Ebola virus.

show abstract

Section: Introductionmentioning

confidence: 99%

Biomimetic Design of Peptide Neutralizer of Ebola Virus with Molecular Simulation

Hou

Zhang

2020

Langmuir

View full text Add to dashboard Cite

show abstract

“…This study was then extended to HCIC ligands on surfaces to evaluate liganddensity effects and to elucidate the binding mechanisms of F C in these systems at various pH conditions. 42 We have recently shown that the MM ligands in free solution have preferential interaction sites in the hinge region and in the C H 2/C H 3 interface on the F C surface and that the binding affinities were in the mM range. 43 While this study showed preferred MM interaction sites on the F C surface, it did not account for protein binding to MM surfaces.…”

Section: Introductionmentioning

confidence: 98%

“…Lin et al employed molecular simulations to identify preferred binding sites of an HCIC ligand on a single-chain F C fragment. This study was then extended to HCIC ligands on surfaces to evaluate ligand-density effects and to elucidate the binding mechanisms of F C in these systems at various pH conditions . We have recently shown that the MM ligands in free solution have preferential interaction sites in the hinge region and in the C H 2/C H 3 interface on the F C surface and that the binding affinities were in the mM range .…”

Section: Introductionmentioning

confidence: 99%

Probing IgG1 F_C–Multimodal Nanoparticle Interactions: A Combined Nuclear Magnetic Resonance and Molecular Dynamics Simulations Approach

et al. 2021

View full text Add to dashboard Cite

In this study, NMR and molecular dynamics simulations were employed to study IgG1 F C binding to multimodal surfaces. Gold nanoparticles functionalized with two multimodal cation-exchange ligands (Capto and Nuvia) were synthesized and employed to carry out solutionphase NMR experiments with the F C . Experiments with perdeuterated 15 N-labeled F C and the multimodal surfaces revealed micromolar residuelevel binding affinities as compared to millimolar binding affinities with these ligands in free solution, likely due to cooperativity and avidity effects. The binding of F C with the Capto ligand nanoparticles was concentrated near an aliphatic cluster in the C H 2/C H 3 interface, which corresponded to a focused hydrophobic region. In contrast, binding with the Nuvia ligand nanoparticles was more diffuse and corresponded to a large contiguous positive electrostatic potential region on the side face of the F C . Results with lower-ligand-density nanoparticles indicated a decrease in binding affinity for both systems. For the Capto ligand system, several aliphatic residues on the F C that were important for binding to the higher-density surface did not interact with the lower-density nanoparticles. In contrast, no significant difference was observed in the interacting residues on the F C to the high-and low-ligand density Nuvia surfaces. The binding affinities of F C to both multimodal-functionalized nanoparticles decreased in the presence of salt due to the screening of multiple weak interactions of polar and positively charged residues. For the Capto ligand nanoparticle system, this resulted in an even more focused hydrophobic binding region in the interface of the C H 2 and C H 3 domains. Interestingly, for the Nuvia ligand nanoparticles, the presence of salt resulted in a large transition from a diffuse binding region to the same focused binding region determined for Capto nanoparticles at 150 mM salt. Molecular dynamics simulations corroborated the NMR results and provided important insights into the molecular basis of F C binding to these different multimodal systems containing clustered (observed at high-ligand densities) and nonclustered ligand surfaces. This combined biophysical and simulation approach provided significant insights into the interactions of F C with multimodal surfaces and sets the stage for future analyses with even more complex biotherapeutics.

show abstract

“…Molecular simulation methods including docking and molecular dynamics (MD) simulation can help to study the binding mechanisms between protein and small molecules, and assist the ligand design for protein separation [25]. Wang et al.…”

Section: Introductionmentioning

confidence: 99%

Rational design of specific ligands for human serum albumin separation and applications

Cai

Zhang

et al. 2020

J of Separation Science

View full text Add to dashboard Cite

Human serum albumin is widely used in clinical practice, and the development of new ligands with high affinity is beneficial to improve its separation efficiency. The Site II of human serum albumin is an active binding site of various molecules such as l‐tryptophan, which was studied with molecular simulation to obtain insights for the design of new ligands. The results showed that the carboxyl and indolyl groups of l‐tryptophan were critical for the binding on Site II. Seven ligands containing carboxyl groups and indolyl groups were designed, and molecular simulation showed that indole‐3‐pentanoic acid was the best ligand. A new ligand combined indole‐3‐acetic acid and cysteine was designed for easier resin preparation, and molecular simulation also indicated that the new ligand bound strongly to Site II. Resins with the new ligand designed was prepared and static adsorption experiments indicated that the new resin had high adsorption capacity of human serum albumin and strong salt tolerance. Finally, recombinant human serum albumin was separated from yeast broth with high purity of 90.4% and recovery of 94.2%, which indicated that the new resin had good adsorption selectivity and strong potential for applications.

show abstract

Molecular insight into protein binding orientations and interaction modes on hydrophobic charge-induction resin

Cited by 16 publications

References 56 publications

Biomimetic Design of Peptide Neutralizer of Ebola Virus with Molecular Simulation

Biomimetic Design of Peptide Neutralizer of Ebola Virus with Molecular Simulation

Probing IgG1 F_C–Multimodal Nanoparticle Interactions: A Combined Nuclear Magnetic Resonance and Molecular Dynamics Simulations Approach

Rational design of specific ligands for human serum albumin separation and applications

Contact Info

Product

Resources

About

Molecular insight into protein binding orientations and interaction modes on hydrophobic charge-induction resin

Cited by 16 publications

References 56 publications

Biomimetic Design of Peptide Neutralizer of Ebola Virus with Molecular Simulation

Biomimetic Design of Peptide Neutralizer of Ebola Virus with Molecular Simulation

Probing IgG1 FC–Multimodal Nanoparticle Interactions: A Combined Nuclear Magnetic Resonance and Molecular Dynamics Simulations Approach

Rational design of specific ligands for human serum albumin separation and applications

Contact Info

Product

Resources

About

Probing IgG1 F_C–Multimodal Nanoparticle Interactions: A Combined Nuclear Magnetic Resonance and Molecular Dynamics Simulations Approach