CLC Drug Discovery Workbench

From Hit to Leadwith the Ligand optimizer

optimizing specific interactions between ligand and binding site is made easier with the Ligand optimizer. Starting from a co-crystallized ligand or a docking re-sult, the Ligand optimizer enables modifications to the ligand in the binding site.

the current ligand interactions with the binding site can be visualized, and areas with hydrogen bond potential are marked. Ligand properties central for druglikeness are automatically evaluated, so that you can focus on new molecular design ideas.

import Protein Structure

Setup Binding Site

Ligand optimizer

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Quick Guide

Binding Site interactions

Ligand Properties

modify Ligand

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Import Protein Structure Protein structures can be downloaded directly to the workbench from the Pro-tein data Bank.

Specify keywords or a PdB id in the search field, and a selection of hits appears below. double-click a hit to open a molecule Project with the content of the PdB file.

Setup Binding Site

the molecules are automatically sorted in categories in the Project tree. From the Project tree, molecules can be hidden or displayed, and their visual repre-sentation can be customized via quick-style buttons.

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the imported protein structure can be set up for ligand binding studies in just two clicks.

the molecule Project now contains a Binding Site Setup.

the Setup Binding Site dialog box is interactive, and the relevant molecules, residues, and interactions will automatically be displayed in the 3d view for easy inspection. the view is continuously updated when changes are made.

molecules sortedin categories

Quick-style buttons

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Ligand Optimizer - Binding Site Interactions

Ligand Optimizer - Ligand Properties

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Select a ligand or docking result in the Project tree and invoke the Ligand optimizer.

the ligand properties are updated when the li-gand is modified. Whenever a property violates Lipinski’s rule of five, it is shown in red.

during ligand optimization, the current interactions with the Binding Site Setup can be visualized in the form of the binding site surface, hydrogen bond interactions only, or all residues and molecules within 5 Å. the green areas on the surface indicate hydrogen bond potential.

during ligand optimization the position and bond rotations of the current ligand can be optimized with respect to the built-in protein-ligand interaction score.

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Ligand Optimizer – Modify Ligand

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Select atoms to be modified on the 2d depiction or in the 3d view. the modifications will automatically adapt to the binding site. the 2d depiction, as well as the binding site interactions, are continuously updated.

Select two atoms to change bond order… Select one atom to change it into another atom type…

… or add a fragment from the built-in libraries or from your own loaded library.

the optimized ligand can be added as a new entry in the Project tree, and compared to the reference.