Modeling of Scaffold Hopping Transformations

Modeling of Scaffold Hopping Transformations

Modeling of Scaffold Hopping Transformations

Combining extensive expertise in computational biophysics and computer-aided drug design, CD BioSciences provides clients with specialist modeling services to calculate the relative protein-ligand binding free energy for scaffold hopping modifications. Our high-quality scientific services will accelerate your research progress in the area of in silico screening of drug-target interactions.


Scaffold hopping, also known as lead hopping, is a strategy for the discovery of structurally novel compounds. This concept comes from computational chemistry and the virtual screening of compounds. It refers to looking for compounds with similar activities but different core structures. Although scaffold hopping has not been around for long, it has already received a great deal of attention in the field of drug discovery. Not only is it applied to projects with known ligands, but also widely used in the optimization of lead compounds.

As a valuable medicinal chemistry design strategy, scaffold hopping also carries significant risks because the vast majority of possible scaffold-hopping modifications may require substantial synthetic effort to achieve and will result in a considerable loss of binding potency. Therefore, it is necessary to develop modeling methods that can predict in advance of chemical resources what new scaffolds are most likely to maintain or improve the potency of a compound, which could significantly reduce the cost and speed up the process of identifying a satisfactory scaffold.

Fig.1 State graph to calculate relative binding free energies. (Ries, 2022)Fig.1 State graph to calculate relative binding free energies. (Ries, 2022)

Our Services

We help our customers to build models to investigate different core hopping transitions (i.e., ring opening/closing, ring size change, ring expansion) and R-group modifications. Our modeling services can be applied to multiple case studies to demonstrate the actual scaffold hopping capabilities of the models. Our services include but are not limited to:

  • Parameter exploration and optimization.
  • Free-energy calculation.
  • Development of new algorithms for molecular scaffold hopping.
  • Quantitative analysis of hopping success rate, bioactivity improvement, uniqueness, efficacy,  diversity and novelty of different approaches.
  • Model training and optimization of hyperparameters.


  • Discovery and optimization of small molecules for innovative drugs.
  • Increasing drug discovery success.
  • Improving the pharmacokinetic properties of molecules.

Our Advantages

  • We have powerful data processing software to provide accurate data analysis for our clients.
  • We have multiple long-term partners and have developed unparalleled expertise in the field of drug discovery.
  • Our excellent research team provides expert advice from start to finish of your projects.

CD BioSciences has been conducting continuous research and studies in the field of drug discovery, particularly in combination with computational biophysics techniques for efficient discovery and optimization of innovative drug small molecules. We provide high-quality modeling services for scaffold hopping transformations and continue to improve the applicability of our models in drug discovery. If you are interested in our services, please contact us for more details.


  1. Ries, B.; et al. Relative free-energy calculations for scaffold hopping-type transformations with an automated RE-EDS sampling procedure. Journal of Computer-Aided Molecular Design. 2022, 1-14.
For research use only, not intended for any clinical use.
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CD BioSciences is a biotechnology company focused on biophysical services. We are proficient in both chemistry and biophysics, and have a comprehensive biophysical platform containing a wide range of advanced technologies.

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