Table of Contents
You can identify new inhibitors/modulators of your target (receptor, enzyme, nucleid acid, etc.) by searching the Mcule database. In Mcule, you can easily build virtual screening workflows by putting together molecular modeling tools like LEGO bricks. Virtual screening workflows are a set of filters and calculations. Filters can eliminate compounds that unlikely bind your target or have other unwanted properties and calculations can rank order the best candidates for example by their estimated binding affinity. You can filter the whole Mcule database (over 5 million compounds) with several tools until you select the most promising compounds (10-1000). You can order the best hits by just a few clicks.
STRUCTURE-BASED VIRTUAL SCREEN
Structure-based virtual screening utilizes the 3D structure of the target when searching for new hits. During the screening, predicted 3D structures of small molecules are fitted into the binding site of the experimentally determined or modeled 3D structure of the target (docking calculation). The 3D structures of thousands of large macromolecules have been already determined by X-ray crystallography or NMR spectroscopy and can be easily selected or uploaded in Mcule. Small molecules predicted to form critical interactions with the target get better (more negative) docking scores and are ranked higher.
LIGAND-BASED VIRTUAL SCREEN
Ligand-based virtual screening does not utilize the 3D structure of the target when searching for new hits. Instead, it is based on the structure of a reference ligand (endogenous ligand, known inhibitor, etc.) that binds to a target and/or exhibits some beneficial effect. In ligand-based virtual screening, compounds are typically ranked based on the similarity to the reference ligand (query).
DIVERSE LIBRARY SELECTION
In Mcule, the input of a structure- or ligand-based virtual screen can be any molecule collection. You can run the virtual screen on the whole Mcule database (over 5 million compounds), but you can also prepare a subset and prefilter the database by different properties and diversity. Running virtual screens on a smaller, properly designed, diverse subset of the full database typically samples the full database sufficiently (finds most chemical scaffolds) and spares time and resources at the same time. The resulting libraries can be also exported and processed further in-house if needed.
You can also build your own workflows for virtual screening, library design or other purposes by putting together molecular modeling tools like LEGO bricks in the Workflow Builder.
The Workflow validation feature helps you to test the efficiency of your built workflows. You can generate a rank ordered list of actives and decoys and the most critical graphs are displayed that helps you judge if the workflow is worth to be executed e.g. to screen the whole Mcule database.