Prof. Jing-Fei Huang, Principle Investigator, Deputy Director, Kunming Institute of Zoology, Chinese Academy of Sciences. The main research interest is focused on the structural and functional evolution of protein families and superfamilies; drug target discovery; evaluation of drug effect, toxic and side-effect. More than 70 papers have been published in Mol. Biol. Evol., FEBS Lett, Structure, Acta Crystall, PLoS ONE, Gene, Proteins, BMC Bioinformatics, BMC Evol Biol, Mol. BioSyst, Bioinformatics and other journals.
1. Molecular dynamics simulation of PNPLA3 with I148M mutation reveals reduced substrate access to the catalytic cavity
A missense mutated I148M in PNPLA3 is significantly correlated with nonalcoholic fatty liver disease (NAFLD). To glean insights into mutation's effect on enzymatic activity, we performed molecular dynamics simulation and flexible docking studies. Our data showed that the size of the substrate-access entry site is significantly reduced in mutants, which limits the access of palmitic acid to the catalytic dyad. Besides, the binding free energy calculations suggest low affinity for substrate to mutant enzyme. The substrate-bound system simulations reveal that the spatial arrangement of palmitic acid is distinct in wild-type from that in mutant. The substrate recognition specificity is lost due to the loop where the I148M mutation was located. Our results provided strong evidence for the mechanism by which I148M affects the enzyme activity.
2. Reconstruction and Analysis of Human Kidney-Specific Metabolic Network
Although kidney plays an essential role in the body, the available kidney-specific model remains incomplete. Our study reveals the reconstruction and characterization of the human kidney metabolic network based on transcriptome and proteome data. A total of 267 potential metabolic biomarkers for kidney-related diseases were successfully explored. Furthermore, we found that the discrepancies in metabolic processes of different tissues are directly corresponding to tissue's functions. Finally, the phenotypes of the differentially expressed genes in diabetic kidney disease were characterized, suggesting that these genes may affect disease development through altering kidney metabolism.
3. The DEER database: a bridge connecting drugs, environmental effects, and regulations
Variability in patient drug responses can be caused by genetic factors and environmental factors (ENFs). Frameworks for understanding the association between ENFs and drug responses are lacking. We constructed a novel database, DEER, for interpretations of chemical ENF effects on drug responses. DEER includes computational predictions of the associations between chemical ENFs and drug responses, currently encompasses 579 drugs, 401 chemical ENFs, and 9247 predicted drug-ENF associations. The entire dataset can be easily queried through a search page. DEER is available at http://bsb.kiz.ac.cn:90/DEER/.
4. Benchmarking Human Protein Complexes to Investigate Drug-Related Systems
Human protein complexes are widely used for protein function annotation, inference of human protein interactome, disease gene prediction, and so on. Therefore, it is highly desired to build an up-to-date catalogue of human complexes to support the research in these applications. We designed a set of concise operations to compile these redundant human complexes and built a comprehensive catalogue called CHPC2012. CHPC2012 achieves a higher coverage for proteins and protein complexes than those individual databases. It is also verified to be a set of complexes with high quality as its co-complex protein associations have a high overlap with protein-protein interactions (PPI) in various existing PPI databases. We demonstrated two distinct applications of CHPC2012. In particular, CHPC2012 provides more insights into drug development. we believe that the CHPC2012 catalogue is able to enhance the studies for protein interactions, protein functions, human diseases, drugs, and related fields of research. Web site: http://www1.i2r.a-star.edu.sg/xlli/CHPC2012/CHPC2012.htm.
Publications in 2013
1. Zhang AD, Dai SX, Huang JF*. Reconstruction and Analysis of Human Kidney-Specific Metabolic Network Based on Omics Data. BioMed Research International, 2013, 2013: doi:10.1155/2013/187509.
2. Yu Q, Huang JF*. The DEER database: A bridge connecting drugs, environmental effects, and regulations. Gene, 2013, 520(2):98-105.
3. Wang J, Zhao YQ, Wang Y, Huang JF*. Molecular dynamics simulations and statistical coupling analysis reveal functional coevolution network of oncogenic mutations in the CDKN2A-CDK6 complex. FEBS Lett, 2013, 587(2):136-141.
4. Wu M, Yu Q, Li X, Zheng J, Huang JF*, Kwoh CK*. Benchmarking human protein complexes to investigate drug-related systems and evaluate predicted protein complexes. PLoS ONE, 2013, 8(2):e53197.
5. Xin YN, Zhao YQ, Lin ZH, Jiang X, Xuan SY, Huang JF*. Molecular dynamics simulation of PNPLA3 I148M polymorphism reveals reduced substrate access to the catalytic cavity. Proteins, 2013, 81(3): 406-414.