Structure-Based Drug Discovery Technology

Structure-Based Drug Discovery Technology

The discovery of lead compounds is an upstream process of drug development, in which computer-aided virtual screening plays a crucial role. From the perspective of drug design, virtual screening has two strategies: ligand-based and structure-based. The two approaches are specific to different use cases and complement each other. In the context of known receptor structures, structure-based virtual screening has demonstrated its utility and reliability, so it is widely used in the field of drug discovery. This screening method, also known as receptor-based virtual screening, mainly uses molecular docking technology to automatically search for binding sites of small molecules to receptors in compound databases based on the three-dimensional structural data of the receptor. Subsequently, a molecular force-field based scoring function is utilized to evaluate potential binding modes, calculate binding energies, and ultimately derive an energetic ranking of the compounds.

 

At CryoEM-Solutions, our structure-based drug discovery technology starts from the target structure, which can be obtained by X-ray, cryo-EM,NMR, or homology modeling methods, and virtualized in a constructed database of compounds using molecular docking techniques. For screening, the binding affinity of ligands and receptors is evaluated through conformational search and scoring functions, and the energy ranking of the compounds is finally obtained. Precision screening is performed through molecular dynamics simulation to obtain target molecules and verified by biological experiments.

 

Figure 1. Structure-Based Drug Design Workflow

 

Why Choose CryoEM-Solutions

1.Cryo-EM structure elucidation

At CryoEM-olutions, our team is at the forefront of global research and application of cryo-EM structure analysis technology. We provide high-resolution, near-native, and fully hydrated protein structures that offer new perspectives for structure-based drug discovery.

 

2.Efficient and flexible computational platform

Dynamically adjusts computational resources according to customer’ needs, providing flexible choices between high-performance computing and cloud computing service models.

 

3.Abundant database resources

CryoEM-olutions has built a computational chemical screening library for medicinal molecules, which greatly improves the success rate of finding active molecules.

 

The Applications of Structure-Based Drug Discovery Technology (SBDD)

While traditional X-ray crystallography is primarily used to resolve protein structures with molecular weights below 100,000 daltons, cryo-EM technology breaks this limitation. The core technology of structure-based and computational drug discovery is applicable to the drug discovery of various drug target structures, especially membrane proteins whose crystal structures are difficult to obtain, such as ion channel proteins, G protein-coupled receptors (GPCRs), and other large molecular weight protein structures.

 

1.GPCR

2.Kinase

3.Nuclear receptor protein

4.Ion channel protein

5.Protease