Computational biosynthesis: Engineer thioesterases for polyketide biosynthesis


    Thioesterases catalyze macrolactonization of polyketides in biosynthesis. Thus, it is expected that engineering thioesterases may vary products. To pursue the most valuable secondary metabolites, we carry out homology modeling upon gene information, and then perform in-silico mutation and simulation. Finally, we will confirm the computation with biochemical experiments.(LJ)


Figure 1. The in-silico complexation of pimaricin and TE.


Theoretical study for molecular mechanism of RNA-induced silencing complex (RISC)


    RNAi (RNA interference) is an RNA-dependent post-transcriptal gene silencing process. Here we explore the molecular mechanism of the P-O-C bond cleavage occuring in RISC. A series of RNA-durg candidates have been investigated with molecular simulations, in order to unveil the relationship between structure and activity.(ZYC)


Figure 2. The calculated structure of duplex RNA and Argonaute protein(RISC)


S-Nitrosohemoglobin: conformational features related to two states


    S-Νitrosylation of β-Cys93 in hemoglobin, forming S-nitrosohemoglobin(SNO-Hb), is of great importance in the process of transportation of nitric oxide (NO), which leads to the regulation of local blood supply through hypoxic vasodilation. We intend to study conformational change of the loop region between T- and R- states after the S-nitrosylation of β-Cys 93, by means of protein modeling and molecular dynamics simulation. This will help to understand molecular mechanism of the state-dependent transportation of NO.(HJW)


Figure 3. The superimpose of β-Cys93 loop structures of T- and R- states, from the molecular simulation.


S-DNA: something changed by thio-modification


    To understand the chiral preference of DNA thio-modification, an in-depth quantum mechanistic calculation has been performed on the models of phosphate diester and dinucleotide. Thio-modification of DNA appear very different conformational features.(LP)


Figure 4. The calculated energy landscape of nomal and thio-modified phosphates

Visualize the chemical reaction of protein S-nitrosylation


    Using quantum chemistry, here we have illustrated electronic structure, geometry, and energy for the reaction between nitric oxide and cysteine, which leads to S-nitrosylation in protein.(LJ)


Figure 5. Reaction map of S-nitrosylation.