Proteins are necessary components of organisms. Research on innovative drug design, enzyme modification and optimization are inseparable from the study of protein structure and function. Relying on national ldquo;863 rdquo;, ldquo;973 rdquo; and NSFC projects, we have systematically carried out drug design and drug metabolism research targeting protein structure. The results are as follows: 1. Drug design of H5N1 virus neuraminidase H5N1 is a subtype of influenza A virus and usually spreads among birds and poultry. However, in the 1990s, it was discovered that it can infect humans and has high pathogenicity and high variability. It has not only become a target of increasing attention in health and epidemic prevention, but has also caused major blows to poultry farming many times in countries around the world. Plant hemagglutinin (H) and neuraminidase (N) on the surface of influenza viruses are currently the main target proteins. We used the neuraminidase crystal structure of N9 virus to build a neuraminidase homologous model of N5, clarified its binding mode with small drug molecules, and explained the structural mechanism by which several mutants develop drug resistance, providing theoretical guidance for the design and development of new drugs targeting H5N1 neuraminidase. 2. Drug design of SARS virus target proteins Severe acute respiratory syndrome (SARS) is a highly fatal infectious disease caused by a new coronavirus. In the early stages of its outbreak, it affected the world, especially my country, because there was no effective treatment. After the structure of its main protease was determined, we quickly completed the design, synthesis and biological activity evaluation of an anti-SARS octapeptide using it as a target. Experiments have proved that the octapeptide preparation has a certain inhibitory effect on the virus, and the strength of the effect is related to the dose. Its median effective concentration (EC50) value is 2 orders of magnitude lower than other drugs, and can be used as a drug lead compound. (Wei Dongqing et al., a polypeptide and its derivatives that inhibit coronavirus rdquo;, Patent No.: ZL200410018679.3) 3. Research on single nucleotide polymorphisms (SNPs) of drug metabolic enzyme CYP450 and development of integrated drug-like prediction software CYP450 is an important metabolic oxidase in the human body, participating in the metabolism of more than 90% of existing drugs. There are a large number of SNP loci in CYP450, which causes varying degrees of differences in expression levels, structure, activity, etc. between different individuals and populations, which is reflected in the significantly different responses to the same drug. We collected data on changes in CYP450 activity caused by SNPs and compiled them into relevant databases, using bioinformatics methods to assist in the screening of drug molecules and the identification of drug lead compounds. At the same time, molecular simulation and structural analysis methods are used to study the changes in the structure and enzyme activity of CYP450 enzyme under the condition of single amino acid mutations, and explore the material basis of the corresponding SNP phenotype, so that the correlation obtained by informatics analysis can be elevated to the molecular structure. Causality and causality have made a preliminary exploration of relevant rules that guide personalized medication and drug design.  The research results of this project were published in JASC (IF= 14.357), the top journal in the international chemical field, as well as journals such as Med Chem and BBRC, providing important guidance for the research field of viral targets and drug design. The total number of other citations in SCIE for the 8 representative articles applied by the project was 637, of which the number of other citations in SCIE for the 8 representative paper was 228.