scholarly journals Mapping Protein–Protein Interactions with Phage-Displayed Combinatorial Peptide Libraries and Alanine Scanning

2014 ◽  
pp. 173-188 ◽  
Author(s):  
Malgorzata E. Kokoszka ◽  
Brian K. Kay
Keyword(s):  
Protein Interactions ◽  
Peptide Libraries ◽  
Protein Protein Interactions ◽  
Alanine Scanning ◽  
Combinatorial Peptide Libraries

scholarly journals Methods for the Creation of Cyclic Peptide Libraries for Use in Lead Discovery

2015 ◽  
Vol 20 (5) ◽  
pp. 563-576 ◽  
Author(s):  
Andrew D. Foster ◽  
James D. Ingram ◽  
Eilidh K. Leitch ◽  
Katherine R. Lennard ◽  
Eliot L. Osher ◽  
...  
Keyword(s):  
Protein Interactions ◽  
High Throughput Screening ◽  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
Peptide Libraries ◽  
Successful Implementation ◽  
Protein Protein Interactions ◽  
Lead Discovery ◽  
Small Molecule Libraries ◽  
The Creation

The identification of initial hits is a crucial stage in the drug discovery process. Although many projects adopt high-throughput screening of small-molecule libraries at this stage, there is significant potential for screening libraries of macromolecules created using chemical biology approaches. Not only can the production of the library be directly interfaced with a cell-based assay, but these libraries also require significantly fewer resources to generate and maintain. In this context, cyclic peptides are increasingly viewed as ideal scaffolds and have proven capability against challenging targets such as protein-protein interactions. Here we discuss a range of methods used for the creation of cyclic peptide libraries and detail examples of their successful implementation.

scholarly journals PPCheck: A Webserver for the Quantitative Analysis of Protein-Protein Interfaces and Prediction of Residue Hotspots

2015 ◽  
Vol 9 ◽  
pp. BBI.S25928 ◽  
Author(s):  
Anshul Sukhwal ◽  
Ramanathan Sowdhamini
Keyword(s):  
Protein Interactions ◽  
Test Cases ◽  
Protein Interface ◽  
Protein Protein Interactions ◽  
Alanine Scanning ◽  
Conserved Residues ◽  
Protein Interfaces ◽  
Computational Alanine Scanning ◽  
Key Residues ◽  
Better Than

Background Modeling protein-protein interactions (PPIs) using docking algorithms is useful for understanding biomolecular interactions and mechanisms. Typically, a docking algorithm generates a large number of docking poses, and it is often challenging to select the best native-like pose. A further challenge is to recognize key residues, termed as hotspots, at protein-protein interfaces, which contribute more in stabilizing a protein-protein interface. Results We had earlier developed a computer algorithm, called PPCheck, which ascribes pseudoenergies to measure the strength of PPIs. Native-like poses could be successfully identified in 27 out of 30 test cases, when applied on a separate set of decoys that were generated using FRODOCK. PPCheck, along with conservation and accessibility scores, was able to differentiate ‘native-like and non-native-like poses from 1883 decoys of Critical Assessment of Prediction of Interactions (CAPRI) targets with an accuracy of 60%. PPCheck was trained on a 10-fold mixed dataset and tested on a 10-fold mixed test set for hotspot prediction. We obtain an accuracy of 72%, which is in par with other methods, and a sensitivity of 59%, which is better than most existing methods available for hotspot prediction that uses similar datasets. Other relevant tests suggest that PPCheck can also be reliably used to identify conserved residues in a protein and to perform computational alanine scanning. Conclusions PPCheck webserver can be successfully used to differentiate native-like and non-native-like docking poses, as generated by docking algorithms. The webserver can also be a convenient platform for calculating residue conservation, for performing computational alanine scanning, and for predicting protein-protein interface hotspots. While PPCheck can differentiate the generated decoys into native-like and non-native-like decoys with a fairly good accuracy, the results improve dramatically when features like conservation and accessibility are included. The method can be successfully used in ranking/scoring the decoys, as obtained from docking algorithms.

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