When there is little or no structural information about the target protein, HitGen CADD experts can perform ligand-based drug design with multiple in silico tools to facilitate the drug discovery process.
Pharmacophore models are generated with both 2D and 3D information of known ligands targeting the protein with appropriate techniques based on projects. New compounds are evaluated by their steric and electrostatic properties with suitable ligand alignment and QSAR methods.
Various scaffold hopping approaches help generate valuable ideas of novel IPs and overcome undesirable properties associated with a structural element.
Potency and ADMET properties of new compounds are predicted with known experimental data and cheminformatics models.
The stable conformation and flexibility of compound structures are predicted with geometry optimization by QM calculation and conformational analysis by MD modeling to help understand their feasibility binding to the target.
In a lot of cases, ligand-based drug design and structure-based drug design can be applied together to develop potent drug candidates. These methods have been applied in different stages and aspects in the research and development at HitGen and benefitted multiple projects.