scholarly journals Single-Molecule Methods for the Large-Scale Characterization of Expression Levels and Protein-Protein Interactions in Shewanella Oneidensis MR-1

2008 ◽  
Author(s):  
Shimon Weiss ◽  
Xavier Michalet
Keyword(s):  
Single Molecule ◽  
Protein Interactions ◽  
Large Scale ◽  
Shewanella Oneidensis ◽  
Protein Protein Interactions ◽  
Expression Levels ◽  
Scale Characterization

Nanopore-based measurement of the interaction of P450cam monooxygenase and putidaredoxin at single-molecule level

2021 ◽  
Author(s):  
Hui Chen ◽  
Yao Lin ◽  
Yi-Tao Long ◽  
Shelley Minteer ◽  
Yi-Lun Ying
Keyword(s):  
Single Molecule ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Single Molecule Level ◽  
P Protein ◽  
Wide Range ◽  
Significant Barrier ◽  
Function Characterization ◽  
Life Function

Protein-protein interactions occur in a wide range of biological processes and are of great significance to life function. Characterization of transient protein-protein interactions remains a significant barrier to our understanding...

Target-Templated de novo Design of Macrocyclic D-/L-Peptides: Inhibitors of the PD-1/PD-L1 Interaction

2020 ◽  
Author(s):  
Salvador Guardiola ◽  
Monica Varese ◽  
Xavier Roig ◽  
Jesús Garcia ◽  
Ernest Giralt
Keyword(s):  
Protein Interactions ◽  
Cyclic Peptides ◽  
General Framework ◽  
Large Scale ◽  
De Novo ◽  
Inhibitory Effect ◽  
Original Text ◽  
Protein Protein Interactions ◽  
Retraction Notice ◽  
Pharmaceutical Properties

<p>NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above.</p><p><br></p><p>------------------------------------------------------------------------</p><p><br></p><p>Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-<i>i</i>3 and PD-<i>i</i>6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our <i>de novo </i>design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.<i></i></p>

Target-Templated de novo Design of Macrocyclic D-/L-Peptides: Inhibitors of the PD-1/PD-L1 Interaction

2020 ◽  
Author(s):  
Salvador Guardiola ◽  
Monica Varese ◽  
Xavier Roig ◽  
Jesús Garcia ◽  
Ernest Giralt
Keyword(s):  
Protein Interactions ◽  
Cyclic Peptides ◽  
General Framework ◽  
Large Scale ◽  
De Novo ◽  
Inhibitory Effect ◽  
Original Text ◽  
Protein Protein Interactions ◽  
Retraction Notice ◽  
Pharmaceutical Properties

<p>NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above.</p><p><br></p><p>------------------------------------------------------------------------</p><p><br></p><p>Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-<i>i</i>3 and PD-<i>i</i>6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our <i>de novo </i>design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.<i></i></p>

scholarly journals Short loop functional commonality identified in leukaemia proteome highlights crucial protein sub-networks

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Sun Sook Chung ◽  
Joseph C F Ng ◽  
Anna Laddach ◽  
N Shaun B Thomas ◽  
Franca Fraternali
Keyword(s):  
Protein Interactions ◽  
Large Scale ◽  
Interaction Network ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Short Loop ◽  
New Strategy ◽  
Loop Network ◽  
Protein Protein Interaction Network

Abstract Direct drug targeting of mutated proteins in cancer is not always possible and efficacy can be nullified by compensating protein–protein interactions (PPIs). Here, we establish an in silico pipeline to identify specific PPI sub-networks containing mutated proteins as potential targets, which we apply to mutation data of four different leukaemias. Our method is based on extracting cyclic interactions of a small number of proteins topologically and functionally linked in the Protein–Protein Interaction Network (PPIN), which we call short loop network motifs (SLM). We uncover a new property of PPINs named ‘short loop commonality’ to measure indirect PPIs occurring via common SLM interactions. This detects ‘modules’ of PPI networks enriched with annotated biological functions of proteins containing mutation hotspots, exemplified by FLT3 and other receptor tyrosine kinase proteins. We further identify functional dependency or mutual exclusivity of short loop commonality pairs in large-scale cellular CRISPR–Cas9 knockout screening data. Our pipeline provides a new strategy for identifying new therapeutic targets for drug discovery.

scholarly journals Remote Sensing Methods for the Biophysical Characterization of Protected Areas Globally: Challenges and Opportunities

2021 ◽  
Vol 10 (6) ◽  
pp. 384
Author(s):  
Javier Martínez-López ◽  
Bastian Bertzky ◽  
Simon Willcock ◽  
Marine Robuchon ◽  
María Almagro ◽  
...  
Keyword(s):  
Remote Sensing ◽  
Protected Areas ◽  
Large Scale ◽  
Anthropogenic Activities ◽  
Global Scale ◽  
Area Network ◽  
Biophysical Characterization ◽  
Challenges And Opportunities ◽  
Scale Characterization

Protected areas (PAs) are a key strategy to reverse global biodiversity declines, but they are under increasing pressure from anthropogenic activities and concomitant effects. Thus, the heterogeneous landscapes within PAs, containing a number of different habitats and ecosystem types, are in various degrees of disturbance. Characterizing habitats and ecosystems within the global protected area network requires large-scale monitoring over long time scales. This study reviews methods for the biophysical characterization of terrestrial PAs at a global scale by means of remote sensing (RS) and provides further recommendations. To this end, we first discuss the importance of taking into account the structural and functional attributes, as well as integrating a broad spectrum of variables, to account for the different ecosystem and habitat types within PAs, considering examples at local and regional scales. We then discuss potential variables, challenges and limitations of existing global environmental stratifications, as well as the biophysical characterization of PAs, and finally offer some recommendations. Computational and interoperability issues are also discussed, as well as the potential of cloud-based platforms linked to earth observations to support large-scale characterization of PAs. Using RS to characterize PAs globally is a crucial approach to help ensure sustainable development, but it requires further work before such studies are able to inform large-scale conservation actions. This study proposes 14 recommendations in order to improve existing initiatives to biophysically characterize PAs at a global scale.

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