Research

Teaching

Publications

Chemoinformatics Research Group

Val Gillet

Professor of Chemoinformatics
Chemoinformatics Research Group,
Information School
University of Sheffield
Phone: 0114 2222 652
Fax: 0114 278 0300
Email: v.gillet@sheffield.ac.uk.

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NEWS

The short course A Practical Introduction to Chemoinformatics is scheduled to run June 21st to June 24th in Sheffield.

Announcing the Sixth Joint Sheffield Conference on Chemoinformatics which will take place July 22-24, 2013 at Sheffield University. More details to follow.

My Research Interests:

I head the Chemoinformatics section of the Computational Information Systems Research Group. My research interests are chemoinformatics and computational approaches to drug design including: de novo design; pharmacophore elucidation; combinatorial library design and diversity analysis; novel molecular descriptors for similarity searching;the identification of structure-activity relationships; and structure-based drug design. I have particular interests in machine learning approaches and applications of evolutionary algorithms.

Current Group Members:

Post-doctoral Researchers

  • Eleanor Gardiner is a post-doc working on probabilistic similarity methods in collaboration with AstraZeneca.
  • Richard Sherhod is a KTP Associate funded by Lhasa Limited and EPSRC working on toxicity prediction.

PhD Students

  • Daniel Butler is working in the area of 3D similarity searching.
  • Sonny Gan who is working on clustering techniques for chemical databases in collaboration with AstraZeneca.
  • Jorge Valencia who is working on target deconvolution for prions in collaboration with Dr. Beining Chen in the Department of Chemistry.
  • James Wallace, working in the area of de novo design in collaboration with Dr. Beining Chen in the Department of Chemistry and Eli Lily.

Previous Group Members:

  • Ben Allen. De novo design in collaboration with the Cambridge Crystallographic Data Centre and Eli Lilly.
  • Iain Mott. Multiobjective optimisation to improve protein-ligand docking. KTP Associate position funded by Novartis and the DTI.
  • Richard Sherhod. Toxicity Prediction. Lhasa Limited. PhD 2011.
  • Georgios Papadatos. Data Mining for Lead Optimisation. EPSRC and GlaxoSmithKline. PhD 2011.
  • Richard Martin. Application of Multi-resolution Approaches to the Representation of Small Molecules. BBSRC and GlaxoSmithKline. PhD 2010.
  • Hina Patel. Development of a De Novo Design Tool. EPSRC and Eli Lilly. PhD 2009. Best Oral Presentation at the Young Modellers Forum in London, 2007 and CINF-IO Informatics Scholarship for Scientific Excellence at the American Chemical Society Meeting, New Orleans, April 2008.
  • Sally Mardikian. Applications of Multiobjective Evolutionary Algorithms to Problems in Bioinformatics. MRC. PhD 2008.
  • Yogi Patel. Searching and Clustering Pharmacological Fingerprints. Janssen Pharmaceuticals. PhD 2008.
  • Kris Birchall. Novel Chemoinformatics Methods for Molecuar Similarity and Diversity Analyses. BBSRC and GlaxoSmithKline. PhD 2007.
  • Tummala Rama Krishna Reddy. Identification of Therapeutic Leads for Prion Diseases. PhD 2007.
  • Kirstin Moffat. The Development of Computational Methods for 3D Similarity and Structure-Based Design Techniques in Lead Optimisation. EPSRC and GlaxoSmithKline. PhD 2006.
  • Illy Khatib and Orazio Nicolotti. The Application of Evolutionary Computing to Drug Design. GlaxoSmithKline Post-docs.
  • Simon Cottrell. Alignment of Multiple Flexible Molecules. EPSRC and the Cambridge Crystallographic Data Centre. PhD 2005.
  • Trudi Wright. Methods for Focussed Combinatorial Library Design, Funded by BBSRC and GlaxoSmithKline. PhD 2004.
  • Ed Barker. Development of Reduced Graphs as Novel Descriptors for Identifying Structure-Activity Relationships. EPSRC and AstraZeneca. PhD 2004.
  • Martin Whittle. Mining Molecular Bioassay Data. Pfizer UK Post-doc. 2004.
  • David Wilton Support Tools for Pharmacophore Identification. Pfizer US Post-doc 2005.

Recent Publications:

Book
  • Leach A.R., Gillet V.J. An Introduction to Chemoinformatics, Revised Edition, Springer, 2007.

Journal Articles

  • Taylor, R., Cole, J.C., Cosgrove, D.A., Gardiner, E.J. Gillet, V.J. Development and Validation of an Improved Algorithm for Overlaying Flexible Molecules. Journal of Computer-Aided Molecular Design. In Press.
  • Martin, R.L., Gardiner, E., Gillet, V.J.,  Senger, S. Compression of Molecular Interaction Fields using Wavelets Thumbnails: Application to Molecular Alignment. Journal of Chemical Information and Modelling.  52, 2012, 757-769. DOI: 10.1021/ci200348h.
  • Papadatos, G., Alkarouri, M., Gillet, V.J., Willett, P., Kadirkamanathan, V., Luscombe, C.N., Bravi, G., Richmond, N.J., Pickett, S.D., Hussain, J., Pritchard, J.M., Cooper, A.W.J., Macdonald S.J.F. Lead Optimisation Using Matched Molecular Pairs: Inclusion of Contextual Information for Enhanced Prediction of hERG Inhibition, Solubility and Lipophilicity. Journal of Chemical Information and Modelling.  50, 2010, 1872-1886. DOI: 10.1021/ci100258p
  • Martin, R.L.; Gardiner, E.; Gillet, V.J.; Munoz-Muriedas, J. & Senger, S. Wavelet Approximation of GRID Fields: Application to Quantitative Structure-Activity Relationships. Molecular Informatics, 29, 2010, 603-620. DOI: 10.1002/minf.201000066.
  • Papadatos, G.; Alkarouri, M.; Gillet, V.J.; Willett, P.; Kadirkamanathan, V.; Luscombe, C.N.; Bravi, G.; Richmond, N.J.; Pickett, S.D.; Hussain, J.; Pritchard, J.M.; Cooper, A.W.J.; Macdonald, S.J.F. Lead Optimization Using Matched Molecular Pairs: Inclusion of Contextual Information for Enhanced Prediction of hERG Inhibition, Solubility, and Lipophilicity. Journal of Chemical Information and Modeling, 50, 2010, 1872-1886. DOI: 10.1021/ci100258p
  • Leach, A.R.; Gillet, V.J.; Lewis, R.A. & Taylor, R. Three-Dimensional Pharmacophore Methods in Drug Discovery. Journal of Medicinal Chemistry, 53, 2010, 539-558. DOI: 10.1021/jm900817u
  • Gardiner, E.J.; Gillet V.J.; Cosgrove D. & Taylor R. Multiobjective Optimisation of Pharmacophore Hypotheses: Bias Towards Low-Energy Conformations. Journal of Chemical Information and Modelling, 49, 2009, 2761-2773. DOI: 10.1021/ci9002816
  • Birchall, K.; Gillet, V.J.; Willett, P.; Ducrot, P. & Lutteman C. Use of Reduced Graphs to Encode Bioisosterism for Similarity-Based Virtual Screening. Journal of Chemical Information and Modelling, 49, 2009, 1330-1346. DOI: 10.1021/ci900078h
  • Patel, H.; Chen, B.; Gillet V.J. & Bodkin, M.J. Knowledge-Based Approach to De Novo Design Using Reaction Vectors. Journal of Chemical Information and Modeling, 49, 2009, 1163-1184. DOI: 10.1021/ci800413m
  • Gardiner, E.J.; Gillet, V.J.; Haranczyk, M.; Hert, J.; Holliday, J.D.; Malim, N.; Patel Y. & Willett , P. Turbo Similarity Searching: Effect of Fingerprint and Dataset on Virtual-Screening Performance. Statistical Analysis and Data Mining, 2, 2009, 103-114.
  • Papadatos, G.; Cooper, A.W.J.; Kadirkamanathan, K.; MacDonald, S.J.F.; McLay, I.M.; Pickett, S.D.; Pritchard, J.M.; Willett, P. & Gillet, V.J., Analysis of Neighbourhood Behaviour in Lead Optimisation and Array Design. Journal of Chemical Information and Modeling, 49, 2009, 195-208. DOI: 10.1021/ci800302g
  • Patel, Y.; Gillet, V.J.; Howe, T.; Pastor, J.; Oyarzabal, J. & Willett, P. Assessment of Additive/Non-Additive Effects in Structure-Activity Relationships: Implications for Iterative Drug Design. Journal of Medicinal Chemistry, 51, 2008, 7552-7562. DOI: 10.1021/jm801070q
  • Birchall, K.; Gillet, V.J.; Harper, G. & Pickett, S.D. Evolving Interpretable Structure-Activity Relationship Models. Part 1: Reduced Graph Queries. Journal of Chemical Information and Modeling 48, 2008, 1543-1557. DOI: 10.1021/ci8000502
  • Birchall, K.; Gillet, V.J.; Harper, G. & Pickett, S.D. Evolving Interpretable Structure-Activity Relationship Models. Part 2: Using Multiobjective Optimisation to Derive Multiple Models. Journal of Chemical Information and Modeling, 48, 2008, 1558-1570. DOI: 10.1021/ci800051h
  • Moffat, K.M.; Gillet, V.J.; Bravi, G. & Leach A.R. A Comparison of Field-Based Similarity Methods. Journal of Chemical Information and Modeling, 48, 2008, 719-729. DOI: 10.1021/ci700130j
  • Gillet, V.J. New Directions in Library Design and Analysis. Current Opinion in Chemical Biology, 12, 2008, 372-378 DOI: 10.1016/j.cbpa.2008.02.015
  • Whittle M.; Eaglestone B.; Ford N.; Gillet V.J. & Madden A. Data Mining of Search Engine Logs. Journal of the American Society for Information Science and Technology, 58, 2007, 2382-2400. DOI: 10.1002/asi.20733
  • Gardiner, E.J.; Gillet, V.J.; Willett, P & Cosgrove, D.A. Representing Clusters Using a Maximum Common Edge Substructure Algorithm Applied to Reduced Graphs and Molecular Graphs. Journal of Chemical Information and Modeling, 47, 2007, 354-366. DOI: 10.1021/ci600444g
  • Cottrell, S.J.; Gillet, V.J. & Taylor, R. Incorporating Partial Matches within Multiobjective Pharmacophore Identification. Journal of Computer-Aided Molecular Design, 20, 2006, 735-749. DOI: 10.1007/s10822-006-9086-7
  • Whittle M.; Eaglestone B.; Ford N.; Gillet V.J. & Madden A., Query Transformations and their Role in Web Searching by the General Public. Information Research, 12, 2006.
  • Whittle, M.; Gillet, V.J.; Willett, P.; Alex, A. & Loesel, J. Analysis of Data Fusion Methods in Virtual Screening: Similarity and Group Fusion. Journal of Chemical Information and Modeling, 46, 2006, 2193-2205. DOI: 10.1021/ci0496144
  • Whittle, M.; Gillet, V.J.; Willett, P.; Alex, A. & Loesel, J. Analysis of Data Fusion Methods in Virtual Screening: Theoretical Model. Journal of Chemical Information and Modeling, 46, 2006, 2206-2219. DOI: 10.1021/ci049615w
  • Ganguly, M.,; Brown, N.; Schuffenhauer, A; Ertl, P.; Gillet, V.J. & Greenidge, P. Introducing the Consensus Modeling Concept in Genetic Algorithms: Application to Interpretable Discriminant Analysis. Journal of Chemical Information and Modeling, 46, 2006, 2110-2124. DOI: 10.1021/ci0505291
  • Birchall, K, Gillet, V.J., Harper, G. & Pickett, S.D. Training Similarity Searches for Specific Activities: Application to Reduced Graphs. Journal of Chemical Information and Modeling, 46, 2006, 577-586. DOI: 10.1021/ci050465e
  • Barker E.; Buttar, D.; Cosgrove, D.; Gardiner, E.; Willett, P. & Gillet, V.J. Scaffold Hopping Using Clique Detection Applied to Reduced Graphs. Journal of Chemical Information and Modeling, 46, 2006, 503-511. DOI: 10.1021/ci050347r
  • Reddy, T.R.K.; Mutter, R.; Heal, W.; Guo, K.; Gillet, V.J.; Pratt, S. & Chen B. Library Design, Synthesis, and Screening: Pyridine Dicarbonitriles as Potential Prion Disease Therapeutics. Journal of Medicinal Chemistry, 49, 2006, 607-615. DOI: 10.1021/jm050610f
  • Kristam, R.; Gillet, V.J.; Lewis, R.A. & Thorner, D. Comparison of Conformational Analysis Techniques to Generate Pharmacophore Hypotheses Using Catalyst. Journal of Chemical Information and Modeling, 45, 2005, 461-476. DOI: 10.1021/ci049731z
  • Cottrell, S.; Gillet, V.J.; Taylor R. & Wilton, D. Generation of Multiple Pharmacophore Hypotheses Using Multiobjective Optimisation Techniques. Journal of Computer-Aided Molecular Design, 18, 2004, 665-682. DOI: 10.1007/s10822-004-5523-7
  • Whittle, M.; Gillet, V.J.; Willett, P.; Alex, A. & Loesel, J. Enhancing the Effectiveness of Virtual Screening by Fusing Nearest Neighbor Lists: A Comparison of Similarity Coefficients. Journal of Chemical Information and Computer Sciences, 44, 2004, 1840-1848. DOI: 10.1021/ci049867x
  • Gillet, V.J. Applications of Evolutionary Computation in Drug Design. Applications of Evolutionary Computation in Chemistry, 110, 2004, 133-152. DOI: 10.1007/b13935
  • Wright, T.; Gillet, V.J.; Green, D.V.S. & Pickett, S.D. Optimising the Size and Configuration of Combinatorial Libraries. Journal of Chemical Information and Computer Sciences, 43, 2003, 381-390. DOI: 10.1021/ci0255836
  • Barker, E.; Gardiner, E.; Gillet, V.J.; Kitts, P. & Morris, J. Further Development of Reduced Graphs for Identifying Bioactive Compounds. Journal of Chemical Information and Computer Sciences, 43, 2003, 346-356. DOI: 10.1021/ci0255937
  • Gillet, V.J.; Willett, P. & Bradshaw, J. Similarity Searching Using Reduced Graphs. Journal of Chemical Information and Computer Sciences, 43, 2003, 338-345. DOI: 10.1021/ci025592e
  • Bishop, N.; Gillet, V.J.; Holliday, J.D. & Willett, P. Chemoinformatics Research at the University of Sheffield: a History and Citation Analysis. Journal of Information Science, 29, 2003, 249-267.
  • Patel, Y.; Gillet, V.J.; Bravi, G. & Leach, A.R. A Comparison of the Pharmacophore Identification Programs: Catalyst, DISCO and GASP. Journal of Computer-Aided Molecular Design, 16, 2002, 693-681.
  • Gillet, V.J. Reactant- and Product-Based Approaches to the Design of Combinatorial Libraries. Journal of Computer-Aided Molecular Design, 16, 2002, 371-380.
  • Nicolotti, O.; Gillet, V.J.; Fleming, P.J. & Green, D.V.S. Multiobjective Optimisation in Quantitative Structure-Activity Relationships: Deriving Accurate and Interpretable QSARs. Journal of Medicinal Chemistry, 45, 2002, 5069-5080. DOI: 10.1021/jm020919o
  • Gillet, V.J.; Khatib, W.; Willett, P.; Fleming, P.J. & Green, D.V.S. Combinatorial Library Design Using a Multiobjective Genetic Algorithm. Journal of Chemical Information and Computer Sciences, 42, 2002, 375-385. DOI: 10.1021/ci010375j
  • Gillet, V.J.; Willett, P.; Fleming, P.J. & Green, D.V.S. Designing Focused Libraries Using MoSELECT. Journal of Molecular Graphics and Modelling. 20, 2002, 491-498.
  • Watson, P.; Willett, P.; Gillet, V.J. & Verdonk, M.L. Calculating the Knowledge-based Similarity of Functional Groups Using Crystallographic Data. Journal of Computer-Aided Molecular Design, 15, 2001, 835-857.
  • Verdonk, M.L.; Cole, J.C.; Watson, P.; Gillet, V.J. & Willett, P. SuperStar: Improved Knowledge-Based Interaction Fields for Protein Binding Sites. Journal of Molecular Biology, 307, 2001, 841-859.
  • Gillet, V.J. & Nicolotti, O. Evaluation of Reactant-Based and Product-Based Approaches to the Design of Combinatorial Libraries. Perspectives in Drug Discovery and Design, 20, 2000, 265-287.
  • Schuffenhauer, A.; Gillet, V.J. & Willett, P. Similarity Searching in Files of 3D Chemical Structures: Analysis of the BIOSTER Database Using 2D Fingerprints and Molecular Field Descriptors. Journal of Chemical Information and Computer Sciences, 40, 2000, 295-307.
  • Gillet, V.J.; Willett, P.; Bradshaw, J. & Green, D.V.S. Selecting Combinatorial Libraries to Optimise Diversity and Physical Properties. Journal of Chemical Information and Computer Sciences, 39, 1999, 169-177.
  • Gillet, V.J.; Willett, P. & Bradshaw, J. Identification Of Biological Activity Profiles Using Substructural Analysis And Genetic Algorithms. Journal of Chemical Information and Computer Sciences, 38, 1998, 165-179.
  • Gillet, V.J.; Willett, P. & Bradshaw, J. The Effectiveness of Reactant Pools for Generating Structurally Diverse Combinatorial Libraries. Journal of Chemical Information and Computer Sciences, 37, 1997, 731-740.
  • Gillet, V.J.; Myatt, G.; Zsoldos, Z. & Johnson, A. P. SPROUT, HIPPO and CAESAR: Tools for De Novo Structure Generation Using Templates. Perspectives in Drug Discovery and Design, 3, 1995, 34-50.