Ligand-based Drug Design

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Ligand-Based Drug Design (LBDD) is an umbrella term for the approaches used in the absence of the target structure information.

New drug candidates are discovered and designed based on the properties and characteristics of known ligands or compounds.

Our computer-aided drug design (CADD) experts use state-of-the-art systems and software to provide tailored solutions to your drug discovery project. Turn complex data into actionable insights that enhance the success and experience of your drug discovery program.

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Unlike structure-based drug design, which relies on the 3D structure of the target, ligand-based approaches focus on the knowledge of the chemical features and structural properties of known ligands that bind to a target protein.

This knowledge can be leveraged to derive a pharmacophore – a 3D arrangement of specific atoms or functional groups in a molecule that is essential for its biological activity and interaction with a target protein or receptor.

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Ligand-based Drug Design Appoach

Ligand-based drug design employs various approaches to discover and design new drug candidates based on the properties and characteristics of known ligands or compounds. Some of the key approaches include:

  • Scaffold Hopping: The idea behind scaffold hopping is to explore alternative core frameworks or scaffolds that retain the desired biological activity while overcoming the limitations related to selectivity, pharmacokinetics, intellectual property or safety profiles.
  • The twin concept to scaffold hopping is bioisostere search, an approach which involves swapping functional groups of a molecule with other functional groups that have similar biological properties.
  • Quantitative Structure-Activity Relationship (QSAR): QSAR involves developing mathematical models that correlate the structural features of a series of compounds with their biological activities, or other properties of interest.
  • Shape-Based Methods: Shape-based methods focus on comparing the ligands based on their shape and electrostatic properties.
  • Virtual Screening: Ligand-based virtual screening involves the computational screening of chemical databases to identify potential ligands that are likely to bind to the target. This can be done using similarity searching, pharmacophore-based searching, or machine learning algorithms to rapidly identify novel potentially active compounds.
  • Conformational Analysis: This approach involves studying the different three-dimensional shapes or conformations that a molecule can adopt due to the rotation of its single bonds. Since molecular shape affects how a compound interacts with its target protein and other molecules, understanding and predicting the various conformations a drug molecule can adopt is essential for designing effective and potent drugs.

These approaches are often used in combination to increase the chances of discovering successful drug candidates.

Find out how Charnwood Discovery can support your drug discovery program.

Computer-Aided Drug Design