Virtual High-Throughput Screening (vHTS) aims to predict the biological activity of a large number of compounds against specific targets or pathways based on computer simulation rather than in a physical laboratory setting. Two typical scenarios: structure- or ligand-based vHTS, assume either the knowledge of the target receptor 3D structure or the existence of possibly wide library of small molecules with already measured activity against the desired end-point.
- structure-based vHTS: given 3D model of the receptor (eg. crystallographic of cryo-electron microscope structure) specialised computer software is employed to predict plausible binding modes of the considered compounds as well as their ranking according to calculated binding free energy. We offer an extensive expertise in such docking & scoring campaigns, including:
- assessment and refinement of the receptor model,
- flittering and standardisation of small molecules libraries,
- selection of suitable docking protocol,
- critical evaluation and interpretation of the results.
- ligand-based vHTS: based on the group of molecules whose biological activity in a certain aspect has been quantified, a mathematical relationship is established between their structural and physicochemical properties and the magnitude of the effect under study. The model is subsequently used to estimate the activity of a large pool of screened compounds. Our expertise in such Quantitative Structure-Activity Relationship (QSAR) modelling includes:
- selection and calculation of relevant molecular descriptors,
- formulation of QSAR models using state of the art machine learning approaches,
- thorough evaluation of the results.
