Virtual screening is an approach to select some promising compounds from compound databases for further experimental activity evaluation based on drug design theory and with the help of computer technology and professional application software. Its purpose is to screen out novel leads from dozens or even millions of molecules. The high-throughput screening (HTS) approach realizes sensitive detection and automatic operation, but its positive rate is low, thus the cost of HTS is relatively high. However, the positive rate of virtual screening is usually around 5%-20%. By combining the results of virtual screening with experimental screening, the latter can be more targeted, has a higher hit rate, thus shortening the research cycle and reducing the cost of drug development. Therefore, virtual screening has become a reliable and relatively inexpensive technical means for lead discovery.
Creative Biostructure has a comprehensive computer-aided drug design (CADD) platform, which enables us to offer custom in silico virtual screening services. The optimized virtual screening procedure can reduce the number of compounds to be experimentally screened, improve the possibility of ideal lead discovery, and reduce the risk of failure of later lead optimization, thereby winning valuable time for your project on the development of novel drugs.
Figure 1. A conceptual figure of in silico virtual screening.
Using the known three-dimensional (3D) structure of the target, analyze its binding site, and then predict the binding conformation of target-ligand complexes by molecular docking. According to the scoring function related to binding energy, protein-ligand binding modes are evaluated and classified, and finally a series of compounds with rational binding modes and high predicted scores are selected from a large number of molecules for subsequent biological activity test. We can restrict the screening process by combining pharmacophore modeling and molecular dynamics (MD) simulations.
This strategy focuses on analyzing structures, physicochemical properties, and structure-activity relationships of compounds with known and unknown activities and establishing the quantitative structure-activity relationship (QSAR) and/or pharmacophore model to predict and screen the activity of novel compounds. It is an important complementary means for molecular docking, and the strategy has the advantages of fast speed and good versatility (not limited by the target structure).
We can also provide a hybrid strategy that integrates target structure information and ligand similarity. In this strategy, structure-based and ligand-based filters are flexibly combined in a hierarchical, parallel or hybrid manner, depending on the specific circumstances of the project.
Creative Biostructure offers flexible virtual drug screening solutions to customers in the global biotechnological and pharmaceutical industries with drug discovery demands. You only need to provide the available information and discuss your specific research requirements with our scientists, and we will screen suitable active compounds to lay a foundation for further biological activity evaluation.