Virtual Screening

Virtual screening (VS) is also called computer screening, which uses the molecular docking software on the computer to simulate the interaction between the target and the drug candidate before biological activity screening, and then calculates the affinity between them. Virtual screening is active compound screening based on small-molecule databases. By using molecular docking between small molecule compounds and drug targets, virtual screening can quickly screen millions of molecules, which greatly reduces the number of experiments, shortens the research cycle, and reduces the cost of drug development. It is reported that the positive rate of virtual screening is 5%-30%. Virtual screening has emerged as a very promising tool for drug development.

Figure 1. Virtual Screening.

Principle of virtual screening

In principle, virtual screening can be divided into two categories, namely receptor-based virtual screening and ligand-based virtual screening.

• Receptor-based virtual screening starts from the three-dimensional structure of the target protein, studies the characteristic properties of the binding site of the target protein and the interaction mode between it and the small molecule compound, and compares the protein and protein according to the affinity score function related to the binding energy. The binding ability of small molecule compounds is evaluated, and finally a compound with a reasonable binding mode and a higher prediction score is selected from a large number of compound molecules for subsequent biological activity testing.
• Ligand-based virtual screening generally uses small molecule compounds with known activity, and searches the compound database for chemical molecular structures that can match it based on the compound’s shape similarity or pharmacophore model. Finally, these selected compounds were experimentally screened.
• Molecular docking is a drug screening method based on the structure of the target protein. Through the molecular docking of the small molecule compound and the target, the score and spatial conformation are comprehensively analyzed.
• Pharmacophore screening is an efficient drug screening method based on small molecule compounds. By analyzing the pharmacodynamic characteristics of one or more active small molecules, it is concluded that the important pharmacophore characteristics that make the molecule active are summarized.

Overall solutions

CD ComputaBio has abundant database resources, high-performance computer servers, and can provide professional molecular docking and virtual screening services. The optimized virtual screening program can reduce the number of compounds to be experimentally screened on a large scale, increase the possibility of ideal lead discovery, shorten the virtual screening service time, and reduce the risk of failure of subsequent lead optimization. According to specific needs, we can tailor cost-effective service plans to provide high-quality early drug development services for our scientific research customers.

AI-based approaches

• Target selection: This is the first step of virtual screening, which is crucial. Small molecule compounds target four large molecules: proteins, polysaccharides, lipids and nucleic acids.
• Prepare compound database: Before starting a new virtual screening, we need to collect all the compound structures of a specific drug target.
• Docking software: currently popular molecular docking software includes Dock, AutoDock, MolDock, Maestro, etc. When we perform high-throughput docking, Linux-based virtual docking always plays an important role.
• Scoring system: Molecular docking is a calculation method that predicts the preferred position of the molecule (ligand) relative to the second molecule (receptor) when two molecules combine to form a stable complex, and then predicts the binding between molecules Strength or binding affinity receptors and ligands. Artificial intelligence (AI) assisted virtual screening is the docking of millions of structurally diverse compounds with specific therapeutic targets. The AI scoring function is used to select the best match from millions of docking results.

Figure 3. AI assisted virtual screening. (Liu B, et al. 2019)