At Eurofins Discovery, our Research Informatics team includes experience in docking, an important computational method used in drug discovery to predict the binding affinity and orientation of small molecules to a target protein. The goal of docking is to identify molecules that can bind tightly to a specific protein and modulate its biological activity as well as to understand the ways in which molecules interact with their target receptor and ways to optimize such interaction by modulating the structures of the ligands.
Docking
Docking works by simulating the physical interactions between the small molecule and the target protein. It involves two main steps:
- Conformational sampling: In this step, the small molecule is positioned in different conformations and orientations around the target protein. This is done using algorithms that explore the conformational space of the small molecule and search for favorable binding modes.
- Scoring and ranking: In this step, the different binding modes are evaluated and scored based on their predicted binding affinity to the target protein. The binding affinity is calculated using energy functions that take into account the van der Waals force, electrostatic, and other interactions between the small molecule and the protein.
We use docking that can be accessed in several stages of drug discovery, including lead identification, lead optimization, and virtual screening. Our team utilizes the latest analytical tools including from OpenEye Scientific Software, Chemical Computing Group, and the Cresset software group to perform docking experiments.
Figure: A view of the crystal structure-derived binding site of Thymidylate Synthase complexed with ligands. The electrostatic and hydrophobic interactions between the ligand and the protein are labeled. These kinds of experimental data are used both in virtual screening as well as in the development of 3D-QSAR models to guide chemistry in the pursuit of new molecules to use as potential new therapies.
