Drug Discovery Services: Structure & Ligand-Based Design Strategies

The advantages of using structural information in drug discovery and design became apparent during the early days of protein X-ray crystallography (Blundell et al. l, 2006, https://doi.org/10.1098/rstb.2005.1800). The two classic examples include the discovery of the AIDS drugs Agenerase and Viracept, developed using the crystal structure of HIV protease (Lapatto et al. 1989, doi:10.1038/342299a0; Miller et al. 1989, DOI: 10.1126/science.2686029) and the influenza drug Relenza, designed using the structure of neuraminidase (Varghese 1999). However, at that time, most pharmaceutical companies were not convinced. They considered the method too expensive and time-consuming for industrial use, leaving the pursuit of structure-based drug discovery to academic groups. All this is history now, and the need for structural information in drug discovery is indisputable.
You may also view our article on how structural biology may help drug discovery.

Planning the services
At the start of a discovery project, we must examine the information available for the target in question. Based on this, we can design a possible strategy. The image to the right shows the combinations of available options:

  • Protein structure known / ligand known - structure-based drug discovery (SBDD) is straightforward.
  • Protein structure known / ligand structure unknown - de novo design.
  • Protein structure unknown / ligand known - use ligand-based drug discovery techniques.
  • Protein structure unknown/ligand unknown - fragment screening, high-throughput screening, etc.
These options are discussed below in more detail. However, you are welcome to contact us directly to discuss our services and to design the most optimal strategy for your project!
Strategies for structure-based drug discovery services
Before the drug discovery and design project starts, depending on the availability of structural data on the protein and its ligands, a project strategy needs to be defined. The image provides a short outline of different options. For details, please see the text on the left.

A blog post also provides a short discussion of strategies from hit identification to structure-based drug discovery.