报告题目:Computer Simulation and Analysis of Proteins: from Study of One Protein at a Time to Analysis of One Million Proteins Together
报 ?告 人:Hong Guo, professor of the Department of Biochemistry & Cellular and Molecular Biology
University of Tennessee and the UT
ORNL Center for Molecular Biophysics of Oak Ridge National Laboratory
In my talk, we will discuss applications of different computational approaches to study proteins in biological systems. We will first show how molecular dynamic (MD) simulations with QM/MM potentials can be applied to understand the catalytic mechanisms of individual enzymes or enzyme complexes as well as their specificity. The early development of the QM/MM approach has led to the Nobel Prize in Chemistry to Karplus, Levitt and Warshel in 2013. The individual enzymes or enzyme complexes that will be discussed include serine-carboxyl peptidases (sedolisins), a variety of methyltransferases (involved in different processes such as lysine and arginine methylations of histones and caffeine biosynthesis), and RING E3-E2 complex for ubiquitin-like NEDD8 transfer. It is demonstrated that these computational approaches can serve as powerful tools for understanding details of enzyme catalysis.
We will then discuss our efforts in collaboration with plant biologists and use of the tools of protein structure prediction to understand proteins and their function. In the last part of my talk, we will discuss how to apply a new approach to make identification, interpretation and extraction of biological insights from proteomes easier. As we know, determination of complete genome sequences from a number of organisms have offered an unprecedented opportunity for biological research and transformed biology into a discipline that depends significantly on how to interpret large-scale data sets. By selecting representative proteomes from three domains of life, two giant DNA viruses, and collective gene sets from viruses and organelles including mitochondria, chloroplast and plasmids, we will show that systematical analyses of the interplay between protein length (L, i.e., the amino acid sequence length) and protein disorder (D, i.e., percentage of residues in a so-called intrinsically disordered state) allow us to construct a two-dimensional LD-space for describing the proteomes or gene sets. It is found that the gene distributions in this LD-space may serve as an architectural “fingerprint” shaped by the evolutionary processes.
Professor Hong Guo is a tenure professor of the Department of Biochemistry & Cellular and Molecular Biology, University of Tennessee and the UT/ORNL Center for Molecular Biophysics of Oak Ridge National Laboratory. ?He obtained his Ph.D degree at Harvard University with the advisor Prof. Martin Karplus (Winner of the Nobel Prize in Chemistry 2013). After that he focused on QM/MM Molecular Simulations to reveal the mechanisms of a variety of enzymatic catalysis, which were published on top journals like Angew. Chem. Int. Ed., Proc. Natl. Acad. Sci. USA, J. Am. Chem. Soc., Chemistry-A European Journal and J. Chem. Theory Comput., with more than 9000 citations by far.