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Biophysics, Structural Biology and Screening (BiSS)
Computational chemistry

Computational chemistry services

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As part of Nor-Openscreen and EU-Openscreen, we offer the following computational chemistry services:

1. HTS analysis - get more value from your screen

Based on the hit list and the compound structures in the screening set, we can analyze your screen to give you information about structure-activity relationships (SAR). This can help you to assess the value of the hit compounds and to guide their further evaluation.

2. Hit expansion - explore SAR

We can screen for analogues of your hit compounds in databases with commercially available compounds. This will help you to quickly explore SAR and to improve the affinities of your hits.

3. Virtual screening - find new ligands

In virtual screening, computer stored compound databases or screened for compounds that are either similar to a query compound or that fit into the binding site of a given target. The goal is the generate a list of compounds which are enriched in ligands.

4. Bespoke services

We also offer other bespoke services, e.g. druggability assessment, homology modeling, and compound design for hit optimization.

 

For all of the services, we have access to an in-house curated library of about 7 million commercially available compounds, to other publicly accessible compound database, in house developed software as well as commercial software packages.

 

For further information and to discuss your needs, contact Ruth Brenk.

 

Selected publications:

  • Sarkar A, Brenk R. To Hit or Not to Hit, That Is the Question - Genome-wide Structure-Based Druggability Predictions for Pseudomonas aeruginosa Proteins. PLoS One 10 (9), e0137279 (2015). [Pubmed | DOI]
  • Brand S, Norcross NR, Thompson S, Harrison JR, Smith VC, Robinson DA, Torrie LS, McElroy SP, Hallyburton I, Norval S, Scullion P, Stojanovski L, Simeons FR, van Aalten D, Frearson JA, Brenk R, Fairlamb AH, Ferguson MA, Wyatt PG, Gilbert IH, Read KD. Lead Optimization of a Pyrazole Sulfonamide Series of Trypanosoma brucei N-Myristoyltransferase Inhibitors: Identification and Evaluation of CNS Penetrant Compounds as Potential Treatments for Stage 2 Human African Trypanosomiasis. J Med Chem 57 (23), 9855-69 (2014). [Pubmed | DOI | F1000 recommended]
  • Daldrop P, Brenk R. Structure-Based Virtual Screening for the Identification of RNA-Binding Ligands. Methods Mol Biol 1103, 127-39 (2014). [Pubmed | DOI]
  • Mok NY, Brenk R, Brown N. Increasing the coverage of medicinal chemistry-relevant space in commercial fragments screening. J Chem Inf Model 54 (1), 79-85 (2014). [Pubmed | DOI | F1000 recommended | practicalfragments.blogspot.co.uk]
  • Urich R, Grimaldi R, Luksch T, Frearson JA, Brenk R, Wyatt PG. The design and synthesis of potent and selective inhibitors of Trypanosoma brucei glycogen synthase kinase 3 for the treatment of human african trypanosomiasis. J Med Chem 57 (18), 7536-49 (2014). [Pubmed | DOI]
  • Mok NY, Maxe S, Brenk R. Locating Sweet Spots for Screening Hits and Evaluating Pan-Assay Interference Filters from the Performance Analysis of Two Lead-like Libraries. J Chem Inf Model 53 (3), 534–44 (2013). [Pubmed | DOI]
  • Urich R, Wishart G, Kiczun M, Richters A, Tidten-Luksch N, Rauh D, Sherborne B, Wyatt PG, Brenk R. De novo design of protein kinase inhibitors by in silico identification of hinge region-binding fragments. ACS Chem Biol 8 (5), 1044-52 (2013). [Pubmed | DOI]
  • Brand S, Cleghorn LA, McElroy SP, Robinson DA, Smith VC, Hallyburton I, Harrison JR, Norcross NR, Spinks D, Bayliss T, Norval S, Stojanovski L, Torrie LS, Frearson JA, Brenk R, Fairlamb AH, Ferguson MA, Read KD, Wyatt PG, Gilbert IH. Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors. J Med Chem 55 (1), 88 (2012). [Pubmed | DOI]
  • Tidten-Luksch N, Grimaldi R, Torrie LS, Frearson JA, Hunter WN, Brenk R. IspE Inhibitors Identified by a Combination of In Silico and In Vitro High-Throughput Screening. PLoS One 7 (4), e35792 (2012). [Pubmed | DOI]
  • Cleghorn LA, Woodland A, Collie IT, Torrie LS, Norcross N, Luksch T, Mpamhanga C, Walker RG, Mottram JC, Brenk R, Frearson JA, Gilbert IH, Wyatt PG. Identification of Inhibitors of the Leishmania cdc-Related Protein Kinase CRK3. ChemMedChem , (2011). [Pubmed | DOI]
  • Daldrop P, Reyes FE, Robinson DA, Hammond CM, Lilley DM, Batey RT, Brenk R. Novel Ligands for a Purine Riboswitch Discovered by RNA-Ligand Docking. Chem Biol 18 (3), 324-35 (2011). [Pubmed | DOI]
  • Krasowski A, Muthas D, Sarkar A, Schmitt S, Brenk R. DrugPred: A Structure-Based Approach To Predict Protein Druggability Developed Using an Extensive Nonredundant Data Set. J Chem Inf Model 51 (11), 2829-42 (2011). [Pubmed | DOI]
  • Mok NY, Brenk R. Mining the ChEMBL Database: An Efficient Chemoinformatics Workflow for Assembling an Ion Channel-Focused Screening Library. J Chem Inf Model 51 (10), 2449-54 (2011). [Pubmed | DOI]
  • Frearson JA, Brand S, McElroy SP, Cleghorn LA, Smid O, Stojanovski L, Price HP, Guther ML, Torrie LS, Robinson DA, Hallyburton I, Mpamhanga CP, Brannigan JA, Wilkinson AJ, Hodgkinson M, Hui R, Qiu W, Raimi OG, van Aalten DM, Brenk R, Gilbert IH, Read KD, Fairlamb AH, Ferguson MA, Smith DF, Wyatt PG. N-myristoyltransferase inhibitors as new leads to treat sleeping sickness. Nature 464 (7289), 728-32 (2010). [Pubmed | DOI | F1000 recommended]
  • Mpamhanga CP, Spinks D, Tulloch LB, Shanks EJ, Robinson DA, Collie IT, Fairlamb AH, Wyatt PG, Frearson JA, Hunter WN, Gilbert IH, Brenk R. One Scaffold, Three Binding Modes: Novel and Selective Pteridine Reductase 1 Inhibitors Derived from Fragment Hits Discovered by Virtual Screening. J Med Chem 52 (14), 4454-65 (2009). [Pubmed | DOI | F1000 recommended | Practical Fragments]
  • Brenk R, Schipani A, James D, Krasowski A, Gilbert IH, Frearson J, Wyatt PG. Lessons Learnt from Assembling Screening Libraries for Drug Discovery for Neglected Diseases. ChemMedChem 3 (3), 435-444 (2008). [Pubmed | DOI]