Autumn Meeting 2009

Jealott’s Hill International Research Centre, Bracknell, UK

The UK QSAR & Chemoinformatics Meeting comes to Syngenta in Jealott’s Hill, Bracknell on Thursday, the 22nd October.

David Leahy (U. Newcastle) will take a high level view of QSAR in terms of comparison of methods. Robin Taylor (Taylor Chemiformatics), Andrew Almond (Conformetrix) and Geoff Skillman (OpenEye) will consider new methods in pharmacophores, shape and bio-isosterism. Oliver Korb (CCDC), Miriam Lopez-Ramos (Syngenta) and Bruck Taddese (Reynold’s group, U. Essex) will discuss applications of docking and protein homology modelling in drug/agrochemical design.


  • Andrew Almond (Conformetrix, UK)
    Computer-aided design with accurate experimental small-molecule shapes [Abstract]
  • Oliver Korb (CCDC, UK)
    Ensemble Docking Revisited [Slides] [Abstract]
  • David E Leahy (University of Newcastle, UK)
    Meta QSAR [Slides] [Abstract]
  • Miriam Lopez-Ramos (Syngenta, UK)
    HPPD: ligand and target based virtual screening on an herbicide target [Slides] [Abstract]
  • Geoff Skillman (OpenEye, UK)
    Bioisosterism and Brood [Abstract]
  • Bruck Taddese (University of Essex, UK)
    Bioinformatics and modeling of putative plant GPCRs [Slides] [Abstract]
  • Robin Taylor (Taylor Cheminformatics Software, UK)
    What can the PDB tell us about pharmacophore elucidation? [Abstract]
  • Bernd Wendt (Elara Pharmaceuticals, UK)
    Mining Public-Source Databases For Structure-Activity Relationships [Slides] [Abstract]


Presentation: Andrew Almond
Computer-aided design with accurate experimental small-molecule shapes

Conformetrix, UK

As computers become faster, it is natural to expect that they will be employed increasingly during hit identification and lead optimisation. However, a persistent barrier to this cost-effective solution is the absence of a general method for predicting accurate small-molecule shape. This critical lack of biologically-relevant, artefact-free 3D data, in part due to complexities of the natural world (e.g., solvent, pH and ions), limits both structure- and ligand-based computeraided design (CADD). Conformetrix offers a unique technology that overcomes these limitations by rapidly and accurately quantifying the aqueous (bioactive) conformation of drugs and natural ligands directly from standard experimental NMR data. We will demonstrate how this approach can be applied to augment existing and future drug-discovery, and facilitate increasingly accurate and reliable CADD.

Presentation: Oliver Korb
Ensemble Docking Revisited

CCDC, UK [Slides]

In recent years, the importance of considering induced fit effects in molecular docking calculations has been widely recognised in the molecular modelling community. While small-scale protein side-chain movements are now accounted for in many state-of-the-art docking strategies, the explicit modelling of large-scale protein motions such as loop movements in kinase domains is still a challenging task. For this reason ensemble-based methods have been introduced taking into account several discrete protein conformations in the conformational sampling step. Our protein-ligand docking approach GOLD1,2 has been extended to search such conformational ensembles time-efficiently. The performance of the approach has been assessed on several protein targets using different scoring functions. A detailed analysis of pose prediction and virtual screening results in dependence of the number of protein structures considered in the conformational ensemble will be presented and limitations of the approach will be highlighted.


  1. Molecular Recognition of Receptor Sites Using a Genetic Algorithm with a Description of Desolvation. G. Jones, P. Willett and R. C. Glen J. Mol. Biol., 245, 43-53, 1995.
  2. Development and Validation of a Genetic Algorithm for Flexible Docking. G. Jones, P. Willett, R. C. Glen, A. R. Leach and R. Taylor, J. Mol. Biol., 267, 727-748, 1997.


Presentation: David E Leahy

University of Newcastle, UK [Slides]

We define Meta QSAR as the comparative study of QSAR modelling techniques and strategies applied across all chemical properties, including the development of metrics for assessing model validation, selection and composition.

Over the last few years we have developed software systems for automatically deriving all possible models from a combination of workflow strategies and modelling techniques which we have called the Discovery Bus. In the last year we have engineered a meta-QSAR analysis process that extracts important information from the model libraries created by the Discovery Bus auto QSAR systems into a meta QSAR database. This database is constantly updated as new data sets are added or modelling components (e.g a new descriptor calculator or modelling method) are added to the Discovery Bus.

Starting from a model library created from data in the WOMBAT database, we have now begin to analyse models in order to compare the performance of components and to compare model performance through metric such as Receiver Operating and Regression Error Characteristic measures. The talk will present a summary of results to date and future directions. A first version of a view of the “Meta QSAR” database can be seen at

Presentation: Miriam Lopez-Ramos
HPPD: ligand and target based virtual screening on an herbicide target

Syngenta, UK [Slides]

Hydroxyphenylpyruvate dioxygenase (HPPD) has proven to be a very successful target for the development of herbicides with bleaching properties, and today HPPD inhibitors are well established in the agrochemical market. Syngenta has a long history of HPPD-inhibitor research, which has led to the synthesis of a large number of compounds, the elucidation a set of HPPD co-crystallised structures and several compounds commercialised.

Since the related data is now on the public domain, HPPD was chosen as a case study for the validation of diverse ligand and target based virtual screening approaches to identify compounds with inhibitory properties.

Presentation: Geoff Skillman
Bioisosterism and Brood

OpenEye, UK


Presentation: Bruck Taddese
Bioinformatics and modeling of putative plant GPCRs

University of Essex, UK [Slides]


Presentation: Robin Taylor
What can the PDB tell us about pharmacophore elucidation?

Taylor Cheminformatics Software, UK

Collating ever bigger and better subsets of the PDB for the purpose of testing protein-ligand docking programs has practically become a cottage industry. So it is curious that, until very recently, correspondingly vigorous efforts have not been made to improve validation standards for pharmacophore elucidation programs, despite the presence in the PDB of many suitable series of protein-ligand structures. In collaboration with the Cambridge Crystallographic Data Centre and the University of Sheffield, the presenter has constructed a new test set (currently comprising 88 structures and 10 different protein-ligand series) for the purpose of testing our multi-objective molecular alignment algorithm. More than anything else, the test set demonstrates just how difficult it is to overlay correctly a set of active molecules. This is principally – though not exclusively – because of the breakdown of the “single binding mode” assumption. In the final analysis, the molecular alignment problem is underdetermined. In all but trivial cases, it is futile to expect that the correct overlay can be identified with confidence, which makes a multi-objective approach particularly appealing.

As is usually the way, the test set has rapidly evolved into a training set, so will be further extended in the next few months.

Presentation: Bernd Wendt
Mining Public-Source Databases For Structure-Activity Relationships

Elara Pharmaceuticals, UK [Slides]

Publicly available chemical biology information as provided by databases such as PubChem or ChemBank has been explored for identification of structure-activity relationships using a set of 255 marketed drugs as queries. The talk will cover a description of the developed approach as well as presentation of some results.