The huge quantity of data that drug discovery generates both externally and internally requires that data informatics is at the heart of any modern research organisation. At Evotec the research informatics department smoothly integrates the disciplines of computational chemistry, bioinformatics, systems integration, data management and support informatics to deliver in silico drug discovery including:
- In silico target identification and drugability assessment
- Virtual screening and hit expansion
- In silico design
These capabilities can be engaged in a standalone capacity or fully integrated with our discovery partners.
In silico Target identification and Drugability assessment
In silico target identification
Evotec uses industry standard target interaction databases which combined with other ‘omics’ data can be used to construct target interaction maps. These networks can be significantly enhanced using our predictive pharmacology tools.
> 200 million bioassay datapoints are currently sourced for model building. Pathway analysis can be used to identify new and novel targets proposed to modulate a disease hypothesis. Such approaches are fundamental in target deconvolution and drug repurposing.
Evotec can run structure-based assessment studies for novel targets to provide an additional read on drugability when no or few druglike compounds are known. New 2D sequence based “switchability” calculations projected onto 3D structures have successfully been used for predicting allosteric sites for modulation, surfaces for PPIs and mAb binding.
Virtual Screening and hit expansion
As part of its large portfolio of screening capabilities, Evotec offers virtual screening and hit expansion campaigns to its customers.
Leveraging a strong expertise in research informatics and in silico design, our scientists will design the most suitable in silico screening campaign to meet our clients’ requirements.
For virtual screening, Evotec has access to multiple methods using the best of-breed commercial software.
The screening campaign can be run using number of compound collections:
- EvoSource (34 million compounds)
- Evotec diverse compound collection (400,000 compounds)
- Sanofi compound collection (700,000 compounds)
- Evotec fragment library (20,000 compounds)
- Evotec diverse phenotypic library (20,000 compounds)
- An annotated druglike library (5,000 compounds)
Chemogenomics and ortholog approaches are also available to our client and provide a good starting point for identifying novel active compounds.
Evotec has licensed LeadIT and Spark for scaffold hopping but also has a number of in-house tools using structure merging and vector placement algorithms.
The hits identified from screening require expansion to provide evidence of SAR. This is traditionally based upon chemical similarity and involves searching databases for ‘like’ molecules. Evotec also uses predictive pharmacology so the molecules that possess a similar target pathway signature can be identified.
Library design, statistical analysis and virtual chemistry tools can be used to design the most information rich set of molecules for synthesis.
In silico design
Evotec possesses significant expertise in QM guided structure-based drug design using the fragment molecular orbital (FMO) approach. FMO calculates the strength of interaction between protein residues and ligand atoms to accurately pinpoint the drivers of molecular affinity.
Molecular simulation (WaterScout) and ΔG (Nautilus) approaches can be applied to identify happy and unhappy waters. Evotec’s large internal HPC (high-performance computing) capacity, employing multiple Intel and GPU clusters, ensures that these approaches are routinely applied.
Designing molecules for the clinic balances the multiple dimensions of medicinal chemistry and pharmacology. Evotec has developed a number of statistical analysis tools for matched-molecular-pair analysis (MMPA) and Free-Wilson approaches. These can be used in combination with predictive modelling tools QSAR, QSPR to enable effective experimental design. PK/PD modelling is done in collaboration with the Evotec DMPK group.