Chemical space visualization, clusterization based on scaffolds and similarity metrics

Chemical Space Visualization, Clusterization Based on Scaffolds and Similarity Metrics

Chemical space is a vast universe of potential molecules that exist in theory, but in reality, only a fraction of these have been synthesized or even explored. The ability to navigate this space efficiently is a crucial task for medicinal chemists, computational chemists, and other researchers trying to discover new drugs and materials. In this blog, we will focus on two methods frequently used for exploring chemical space: scaffold-based clusterization and similarity metrics. We will also discuss the role of 2D and 3D visualization in understanding and navigating chemical space.

Scaffold-Based Clusterization

Scaffold-based clusterization is a technique that groups related molecules based on their structural frameworks, also known as scaffolds. Scaffolds are molecular frameworks that are modified with different functional groups to create a diverse set of molecules. By clustering molecules based on their scaffolds, researchers can rapidly explore the properties and activities that vary within the same scaffold and between different scaffolds. This approach allows researchers to identify promising scaffolds for further optimization and also to understand the impact of specific functional groups on biological activity.

Similarity Metrics

Similarity metrics are mathematical tools used to quantify how similar or dissimilar two molecules are. Similarity metrics are used to create similarity matrices, which are used to cluster molecules based on their structural similarity. Similarity metrics allow researchers to quickly compare molecules to one another and identify promising leads that are structurally related to known active compounds. Similarity metrics are also used to optimize the physicochemical properties of a molecule while retaining its structural features. This approach reduces the cost and time required for synthesis and drug development.


Visualization is an essential tool for exploring and communicating the vast and complex chemical space. 2D visualization is a popular method for viewing molecular structures because it allows researchers to see the chemical functionality and make comparisons between molecules. 2D visualization is also useful for generating diagrams that illustrate the clustering of molecules based on their scaffolds or similarity metrics. 3D visualization is becoming more popular because it allows researchers to explore the conformational flexibility of molecules and understand the binding properties of active molecules with their receptors.


Chemical space is vast and complex, and there are many different approaches for exploring it. Scaffold-based clusterization, similarity metrics, and visualization are useful tools for navigating chemical space and identifying promising molecules for further study. By using these techniques, researchers can accelerate the drug discovery process and ultimately develop more effective treatments for patients.