Molecular basis of a redox switch: molecular dynamics simulations and surface plasmon resonance provide insight into reduced and oxidised angiotensinogen

Angiotensinogen fine-tunes the tightly controlled activity of the renin-angiotensin system by modulating the release of angiotensin peptides that control blood pressure. One mechanism by which this modulation is achieved is via angiotensinogen’s Cys18 – Cys138 disulfide bond that acts as a redox switch. Molecular dynamics simulations of each redox state of angiotensinogen reveal subtle dynamic differences between the reduced and oxidised forms, particularly at the N-terminus. Surface plasmon resonance data demonstrate that the two redox forms of angiotensinogen display different binding kinetics to an immobilised anti-angiotensinogen monoclonal antibody. Mass spectrometry mapped the epitope for the antibody to the N-terminal region of angiotensinogen. We therefore provide evidence that the different redox forms of angiotensinogen can be detected by an antibody-based detection method.

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Molecular basis of HHQ biosynthesis: molecular dynamics simulations, enzyme kinetic and surface plasmon resonance studies

BMC Biophysics ◽

10.1186/2046-1682-6-10 ◽

2013 ◽

Vol 6 (1) ◽

pp. 10 ◽

Cited By ~ 7

Author(s):

Anke Steinbach ◽

Christine K Maurer ◽

Elisabeth Weidel ◽

Claudia Henn ◽

Christian Brengel ◽

...

Keyword(s):

Molecular Dynamics ◽

Surface Plasmon Resonance ◽

Molecular Dynamics Simulations ◽

Surface Plasmon ◽

Plasmon Resonance ◽

Molecular Basis ◽

Enzyme Kinetic ◽

Dynamics Simulations

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Heparin-Sclerostin Interactions from Surface Plasmon Resonance and Molecular Dynamics Simulations

Biophysical Journal ◽

10.1016/j.bpj.2015.11.2912 ◽

2016 ◽

Vol 110 (3) ◽

pp. 544a

Author(s):

J. Joel Janke ◽

Fuming Zhang ◽

Robert J. Linhardt ◽

Angel E. Garcia

Keyword(s):

Molecular Dynamics ◽

Surface Plasmon Resonance ◽

Molecular Dynamics Simulations ◽

Surface Plasmon ◽

Plasmon Resonance ◽

Dynamics Simulations

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PD-1-Targeted Discovery of Peptide Inhibitors by Virtual Screening, Molecular Dynamics Simulation, and Surface Plasmon Resonance

Molecules ◽

10.3390/molecules24203784 ◽

2019 ◽

Vol 24 (20) ◽

pp. 3784 ◽

Cited By ~ 2

Author(s):

Yuanqiang Wang ◽

Haiqiong Guo ◽

Zhiwei Feng ◽

Siyi Wang ◽

Yuxuan Wang ◽

...

Keyword(s):

Molecular Dynamics ◽

Cell Death ◽

Surface Plasmon Resonance ◽

Virtual Screening ◽

Programmed Cell Death ◽

Surface Plasmon ◽

Small Molecule ◽

Plasmon Resonance ◽

Small Molecule Inhibitors ◽

Dynamics Simulation

The blockade of the programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway plays a critical role in cancer immunotherapy by reducing the immune escape. Five monoclonal antibodies that antagonized PD-1/PD-L1 interaction have been approved by the Food and Drug Administration (FDA) and marketed as immunotherapy for cancer treatment. However, some weaknesses of antibodies, such as high cost, low stability, poor amenability for oral administration, and immunogenicity, should not be overlooked. To overcome these disadvantages, small-molecule inhibitors targeting PD-L1 were developed. In the present work, we applied in silico and in vitro approaches to develop short peptides targeting PD-1 as chemical probes for the inhibition of PD-1–PD-L1 interaction. We first predicted the potential binding pocket on PD-1/PD-L1 protein–protein interface (PPI). Sequentially, we carried out virtual screening against our in-house peptide library to identify potential ligands. WANG-003, WANG-004, and WANG-005, three of our in-house peptides, were predicted to bind to PD-1 with promising docking scores. Next, we conducted molecular docking and molecular dynamics (MD) simulation for the further analysis of interactions between our peptides and PD-1. Finally, we evaluated the affinity between peptides and PD-1 by surface plasmon resonance (SPR) binding technology. The present study provides a new perspective for the development of PD-1 inhibitors that disrupt PD-1–PD-L1 interactions. These promising peptides have the potential to be utilized as a novel chemical probe for further studies, as well as providing a foundation for further designs of potent small-molecule inhibitors targeting PD-1.

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