Structure based drug design (SBDD) is a drug design method based on molecular recognition from the three-dimensional structure of ligands and targets. According to drugs and their targets, such as receptors, enzymes, ion channels, nucleic acids, antigens and viruses, we can find and design reasonable drug molecules.
Generally, the steps of SBDD include protein structure preparation, binding site recognition, ligand library preparation, docking and scoring function.
Target is the prerequisite of drug design. The selection of reasonable drug target directly determines the success or failure of drug development. The three-dimensional structure of the target can often be obtained by computer model methods such as X-ray crystallography, multi-dimensional nuclear magnetic resonance or homologous protein structure prediction. Secondly, the interaction model between drug and receptor is measured by experimental means or studied by computational method, and the rational drug design is carried out on this basis; In addition to considering the structural characteristics of drugs and receptors, it is also necessary to consider the influence of factors such as drug solubility, toxicity and metabolic process. Reasonable drug design usually requires 10-15 cycles to find the "most suitable" drug molecules.
1. Advantages: low screening cost. Candidate drugs can be obtained from a small number of compounds; It can significantly improve the hit rate of drug discovery; It can directly predict the drug receptor binding energy.
2. Deficiency: This design requires a complete and clear three-dimensional structure of the target; it only considers the binding strength of the drug and the receptor, and cannot predict the efficacy of the drug; the speed is slow.