Virtual screening, also known as computer screening, refers to the use of molecular docking software on the computer to simulate the interaction between the target and candidate drugs before biological activity screening, and calculate the affinity between the two, so as to reduce the actual number of screened compounds and improve the efficiency of lead compound discovery. Virtual screening as an important branch of the development of drug design, through the theoretical calculation and analysis mass ligand molecular receptor macromolecules and the combination of model, and USES the scoring function scores, choose to find the candidate ligands may effectively, avoids the blindness of compound screening, thereby significantly reducing the cost of finding active lead compounds.
There are many kinds of them, such as GPCR Screening, Ion Channel Screening Service, Transporter Screening Service,(Ion channels are controllable, water-filled pores formed by membrane proteins that help establish and control the potential across membranes by controlling the flow of active ions between the intracellular and extracellular environments. As a key component of rapidly changing cellular processes, such as heart/bone/smooth muscle contraction and epithelial transport of nutrients, ion channels are important therapeutic targets for a range of diseases, such as heart, CNS, immune system and metabolic diseases. With the development of screening technology, the pharmaceutical field has shown more and more interest in the role of ion channels in target validation, efficacy determination, selective analysis and lead optimization.)
In principle, virtual screening can be divided into two categories: receptor-based virtual screening and ligand-based virtual screening.
Virtual screening based on receptor from the three-dimensional structure of target protein, the study of the characteristics of target protein binding sites properties and it has to do with the interaction between small molecular compound model, according to the affinity scoring function related to the binding energy of the combination of protein and small molecule compounds ability evaluation, finally combining picked out from a significant number of compounds in the molecular model is reasonable and higher scores predict compounds, used in the subsequent biological activity test.
Virtual screening based on ligand generally USES small molecule compounds with known activity to search the chemical molecular structure that can match it in the compound database according to the shape similarity of the compound or the pharmacophore model. Finally, these compounds were selected for experimental screening study.
Molecular docking is a drug screening method based on target protein structure. By small molecular compounds and targets for molecular docking, comprehensive analysis of scoring and space conformation, including electrostatic interaction, hydrogen bonding, hydrophobic effect, van der Waals effects, such as nature, small molecules can explore ligand and receptor macromolecules functional mode and combining configuration, explain why the activity of compounds, to provide reasonable optimization of the structure of compound guidance; The potential active compounds can also be screened for reference.
Pharmacophore screening is an efficient drug screening method based on small molecule compounds. By analyzing the pharmacodynamic characteristics of one or more small active molecules, the important pharmacophore characteristics that make the molecules active are deduced. The calculation of pharmacophore screening is small and can be done before molecular docking, and it only takes a short time to screen pharmacophore from millions or tens of millions of small molecular databases. The customer only needs to provide one or more active molecules to construct a public pharmacophore for screening, searching for small molecules with the same characteristics, and guiding the synthesis of new active molecules.
In molecular docking, pharmacophore screening or shape similarity screening, generally choose a variety of small molecule database, ZINC free database contains ChemBridge, Enamine and PubChem and many other compound data, all free to download and download the data of a single supplier. It includes fragment library, drug-like library, drug library and natural product library. Baiham biotechnology provides download services and small molecule optimization work, and the construction of natural products database, Chinese medicine database, drug library, etc., these compounds contain suppliers, molecular weight, rotable bond number, hydrogen bond receptor and donor information.