Virtual Screening

Virtual Screening (VS) plays a key role in Computer Aided Drug Design (CADD), which aims to find potential drug molecules that interact with specific protein pockets from a huge compound library through computational methods.The effectiveness of this approach in screening drugs has been fueled by the rise of advanced computing power and the availability of large-scale biomolecular datasets, which have accelerated the process of drug discovery.

Virtual screening is the screening of active compounds based on small molecule databases.By using molecular docking operations between small molecule compounds and drug targets, virtual screening can quickly select active compounds with drugability from tens to millions of molecules, greatly reducing the number of experimental screening compounds, shortening the research cycle, and reducing the cost of drug development. It is reported that the positive rate of virtual screening is 5%-30%. The number of cases of successful drug design assisted by virtual screening is increasing year by year. Virtual screening has become the most promising drug development tool at present.

Virtual screening process

Virtual screening methods are mainly divided into two types: structure-based virtual screening (SBVS) based on the structure of receptor biomacromolecules and ligand-based virtual screening (LBVS) based on small molecule ligands.

• SBVS receptor-based virtual screening: Receptor-based virtual screening is also called molecular docking-based virtual screening. It is based on the three-dimensional structure of the receptor biological macromolecule determined experimentally or homologously modeled. Through the method of molecular docking, the binding conformation of the small molecule and the receptor is determined, and the binding ability of the protein and small molecule compound is evaluated according to the affinity scoring function related to the binding energy. Finally, the compounds with more reasonable binding modes and higher predicted scores are selected from a large number of compound molecules for subsequent biological activity tests.
• LBVS Ligand-Based Virtual Screening：Ligand-based virtual screening, also known as virtual screening based on pharmacophore models, is based on the analysis of the structure, physicochemical properties and activity relationship of existing drugs to establish a quantitative structure-activity relationship or pharmacophore model to predict the activity of new compounds.

In the past, medicinal chemists focused on the binding affinity between drug molecules and targets and the accurate binding posture. However, as the size of compound libraries continues to increase, the computational cost and screening efficiency of such traditional methods have become limiting factors. However, virtual screening uses computational methods to quickly search large-scale compound libraries, greatly improving the efficiency of drug discovery. Compared with laboratory screening, it is less expensive and can find candidate drugs in a shorter time. In recent years, experts have gradually defined virtual screening as an information retrieval task.That is, similarity matching is used to determine the degree of relevance of a molecule to a given protein pocket, that is, to screen out molecules from the compound library that are most similar to the target pocket and have the potential to bind.Compared with traditional methods of predicting binding affinity or determining binding posture, this method focuses more on the similarity of potential binding molecules to improve the accuracy and efficiency of screening.

References

【1】https://www.medchemexpress.cn/virtual-screening.html