scholarly journals In Silico Peptide-Directed Ligand Design Complements Experimental Peptide-Directed Binding for Protein-Protein Interaction Modulator Discovery

2020 ◽  
Author(s):  
Lesley A. Howell ◽  
Andrew Beekman
Keyword(s):  
Protein Interaction ◽  
In Silico ◽  
Ligand Design ◽  
Cellular Activity ◽  
Protein Protein Interaction ◽  
Hit Rate

Using the protein-protein interaction of Mcl-1/Noxa, two methods for efficient modulator discovery are directly compared. In silico peptide-directed ligand design is evaluated against experimental peptide-directed, allowing for the discovery of two new inhibitors of Mcl-1/Noxa with cellular activity. In silico peptide-directed ligand design demonstrates an in vitro hit rate of 80%. The two rapid and efficient methods demonstrate complementary features for protein-protein interaction modulator discovery.

scholarly journals In Silico Peptide-Directed Ligand Design Complements Experimental Peptide-Directed Binding for Protein-Protein Interaction Modulator Discovery

2020 ◽  
Author(s):  
Lesley A. Howell ◽  
Andrew Beekman
Keyword(s):  
Protein Interaction ◽  
In Silico ◽  
Ligand Design ◽  
Cellular Activity ◽  
Protein Protein Interaction ◽  
Hit Rate

Using the protein-protein interaction of Mcl-1/Noxa, two methods for efficient modulator discovery are directly compared. In silico peptide-directed ligand design is evaluated against experimental peptide-directed, allowing for the discovery of two new inhibitors of Mcl-1/Noxa with cellular activity. In silico peptide-directed ligand design demonstrates an in vitro hit rate of 80%. The two rapid and efficient methods demonstrate complementary features for protein-protein interaction modulator discovery.

scholarly journals Correction: Identification of selective protein–protein interaction inhibitors using efficient in silico peptide-directed ligand design

2019 ◽  
Vol 10 (22) ◽  
pp. 5849-5850
Author(s):  
Andrew M. Beekman ◽  
Marco M. D. Cominetti ◽  
Samuel J. Walpole ◽  
Saurabh Prabhu ◽  
Maria A. O’Connell ◽  
...  
Keyword(s):  
Protein Interaction ◽  
In Silico ◽  
Ligand Design ◽  
Protein Protein Interaction

Correction for ‘Identification of selective protein–protein interaction inhibitors using efficient in silico peptide-directed ligand design’ by Andrew M. Beekman et al., Chem. Sci., 2019, DOI: 10.1039/c9sc00059c.

scholarly journals Identification of selective protein–protein interaction inhibitors using efficient in silico peptide-directed ligand design

2019 ◽  
Vol 10 (16) ◽  
pp. 4502-4508 ◽  
Author(s):  
Andrew M. Beekman ◽  
Marco M. D. Cominetti ◽  
Samuel J. Walpole ◽  
Saurabh Prabhu ◽  
Maria A. O'Connell ◽  
...  
Keyword(s):  
Success Rate ◽  
Protein Interaction ◽  
In Silico ◽  
Ligand Design ◽  
Protein Protein Interaction ◽  
Anticancer Target

Development of selective hDM2/X p53 inhibitors is key to further develop this anticancer target. This method displayed a 50% success rate and identified hDMX selective compounds.

scholarly journals In silico peptide-directed ligand design complements experimental peptide-directed binding for protein–protein interaction modulator discovery

2021 ◽  
Author(s):  
Lesley Ann Howell ◽  
Andrew Michael Beekman
Keyword(s):  
Protein Interaction ◽  
In Silico ◽  
Ligand Design ◽  
Protein Protein Interaction

Using the protein–protein interaction of Mcl-1/Noxa, two methods for efficient modulator discovery are directly compared.

scholarly journals Protein-Protein Interaction Detection: Methods and Analysis

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
V. Srinivasa Rao ◽  
K. Srinivas ◽  
G. N. Sujini ◽  
G. N. Sunand Kumar
Keyword(s):  
Protein Interaction ◽  
Protein Function ◽  
In Silico ◽  
Affinity Purification ◽  
Phylogenetic Profile ◽  
Detection Methods ◽  
Protein Protein Interaction ◽  
Interaction Detection

Protein-protein interaction plays key role in predicting the protein function of target protein and drug ability of molecules. The majority of genes and proteins realize resulting phenotype functions as a set of interactions. The in vitro and in vivo methods like affinity purification, Y2H (yeast 2 hybrid), TAP (tandem affinity purification), and so forth have their own limitations like cost, time, and so forth, and the resultant data sets are noisy and have more false positives to annotate the function of drug molecules. Thus, in silico methods which include sequence-based approaches, structure-based approaches, chromosome proximity, gene fusion, in silico 2 hybrid, phylogenetic tree, phylogenetic profile, and gene expression-based approaches were developed. Elucidation of protein interaction networks also contributes greatly to the analysis of signal transduction pathways. Recent developments have also led to the construction of networks having all the protein-protein interactions using computational methods for signaling pathways and protein complex identification in specific diseases.

scholarly journals Definition of a minimal munc18c domain that interacts with syntaxin 4

2000 ◽  
Vol 350 (3) ◽  
pp. 741-746 ◽  
Author(s):  
Julian GRUSOVIN ◽  
Violet STOICHEVSKA ◽  
Keith H. GOUGH ◽  
Katrina NUNAN ◽  
Colin W. WARD ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Full Length ◽  
Yeast Two Hybrid ◽  
Protein Protein Interaction ◽  
Interaction Studies ◽  
Syntaxin 4 ◽  
Definition Of ◽  
Two Hybrid

munc18c is a critical protein involved in trafficking events associated with syntaxin 4 and which also mediates inhibitory effects on vesicle docking and/or fusion. To investigate the domains of munc18c responsible for its interaction with syntaxin 4, fragments of munc18c were generated and their interaction with syntaxin 4 examined in vivo by the yeast two-hybrid assay. In vitro protein–protein interaction studies were then used to confirm that the interaction between the proteins was direct. Full-length munc18c1–592, munc18c1–139 and munc18c1–225, but not munc18c226–592, munc18c1–100, munc18c43–139 or munc18c66–139, interacted with the cytoplasmic portion of syntaxin 4, Stx42–273, as assessed by yeast two-hybrid assay of growth on nutritionally deficient media and by β-galactosidase reporter induction. The N-terminal predicted helix-a-helix-b-helix-c region of syntaxin 4, Stx429–157, failed to interact with full-length munc18c1–592, indicating that a larger portion of syntaxin 4 is necessary for the interaction. The yeast two-hybrid results were confirmed by protein–protein interaction studies between Stx42–273 and glutathione S-transferase fusion proteins of munc18c. Full-length munc18c1–592, munc18c1–139 and munc18c1–225 interacted with Stx42–273 whereas munc18c1–100 did not, consistent with the yeast two-hybrid data. These data thus identify a region of munc18c between residues 1 and 139 as a minimal domain for its interaction with syntaxin 4.

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