Pharmacophore Modeling

When the ligand interacts with the macromolecular target, the active conformation with geometric and energy matching with the target should be generated. The pharmacophore is regarded as the greatest common denominator of the molecular interaction characteristics shared by a group of active molecules. Each type of atom or group in the ligand that exhibits certain properties associated with molecular recognition can be mapped to pharmacophore features, such as hydrophobic regions, hydrogen bond acceptors/donors, aromatic ring systems, negatively ionizable groups, positively ionizable groups, and any possible combination.

Pharmacophore modeling is a multifunctional subfield of computer-aided drug design (CADD). With the advanced CADD platform, Creative Biostructure can offer the pharmacophore modeling solution, which has many diverse applications in drug discovery programs, for instance, change the scaffold into novel compounds with a similar target, assist in virtual screening for new inhibitors, perform compound ADME/Tox analysis, and study possible off-targets.

Pharmacophore modeling approaches based on the available data.  Figure 1. Pharmacophore modeling approaches based on the available data. (Schaller D.; et al. 2020)

Based on the information available in a project, there are two basic approaches for pharmacophore modeling:

  • Ligand-based pharmacophore modeling

This approach has become a crucial computational strategy to facilitate drug discovery when the macromolecular target structure is unknown. The pharmacophore model is obtained by superimposing the structures of a set of active molecules and extracting the common chemical features critical to the interaction between the ligand and the specific macromolecular target.

  • Receptor-based pharmacophore modeling

This approach is directly related to the 3D structure of the target or the target-ligand complex and obtains the pharmacophore model by detecting the possible interaction sites between the target and the ligand, involving the analysis of complementary chemical features and spatial relationships of the active sites, and subsequent assembly of a pharmacophore model with selected features. According to the known information of a project, we can implement this strategy based on target-ligand complexes or target macromolecules (without ligands).

Our Pharmacophore Modeling can help you:

  • Identify the key pharmacophore features of bioactive molecules to establish clear structure-activity relationships (SAR).
  • Virtual screen compound libraries through the pharmacophore method to discover new scaffold-based compounds with biological activity against their target.
  • De novo design and construct a novel lead compound that meets the requirements of a given pharmacophore.
  • Predict adverse reactions of a lead compound in the early stages of drug development by using the pharmacophore model.
  • Perform target-fishing with the pharmacophore model.

Capabilities and advantages of our Pharmacophore Modeling services:

  • The determination of the 3D structure of targets and target-ligand complexes is our specialty.
  • High-performance computing equipment and tools support ligand conformation analysis, bioactive conformation analysis, and pharmacophore query.
  • We can utilize pharmacophore models to guide molecular docking to improve virtual screening.
  • We can combine 3D pharmacophore models with molecular dynamics (MD) simulations to show a physiologically relevant dynamic interaction pattern.
  • Flexible and customized solutions that can be combined with applications such as virtual screening, de novo design, lead optimization, multi-target drug design, activity analysis, and target identification.

Creative Biostructure's pharmacophore modeling solution has been successfully applied to virtual screening and optimization processes for targeted GPCRs. Our drug discovery experts will evaluate and design cost-effective solutions before the project starts. In addition, our CADD platform supports comprehensive drug discovery programs.


  1. Qing X.; et al. Pharmacophore modeling: advances, limitations, and current utility in drug discovery. Journal of Receptor, Ligand and Channel Research. 2014, 7: 81-92.
  2. Schaller D.; et al. Next generation 3D pharmacophore modeling. Wiley Interdisciplinary Reviews: Computational Molecular Science. 2020: e1468.
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