Taehwan Jang’s research while affiliated with Korea Advanced Institute of Science and Technology and other places

Solid–liquid interfaces are ubiquitous in scientifically and technologically important systems, and they govern complex chemophysical processes such as those in electrochemistry and heterogeneous catalysis. Atomic-level elucidation of interfacial structures has been extensively pursued; however, related research is still limited. A major obstacle lies in the intrinsic character of interfaces: they are located between two bulk phases that make the application of spectroscopic or surface-science techniques be difficult. Although this suggests the possibility of employing computational approaches to explore interfacial structures, modern molecular simulation methods suffer from an inability to simulate large interfacial systems in a sufficient time scale at the all-atom resolution. To develop a method capable of simulating solid–liquid interfaces, we have been developing a mean-field quantum mechanics/molecular mechanics (QM/MM) method. This Review briefly summarizes the theoretical background of mean-field QM/MM, as well as recent efforts to advance it. Furthermore, we summarize several studies performed based on this method.

The design of small molecules that inhibit disease-relevant proteins represents a longstanding challenge of medicinal chemistry. Here, we describe an approach for encoding this challenge—the inhibition of a human drug target—into a microbial host and using it to guide the discovery and biosynthesis of targeted, biologically active natural products. This approach identified two previously unknown terpenoid inhibitors of protein tyrosine phosphatase 1B (PTP1B), an elusive therapeutic target for the treatment of diabetes and cancer. Both inhibitors target an allosteric site, which confers unusual selectivity, and can inhibit PTP1B in living cells. A screen of 24 uncharacterized terpene synthases from a pool of 4,464 genes uncovered additional hits, demonstrating a scalable discovery approach, and the incorporation of different PTPs into the microbial host yielded alternative PTP-specific detection systems. Findings illustrate the potential for using microbes to discover and build natural products that exhibit precisely defined biochemical activities yet possess unanticipated structures and/or binding sites.

The design of small molecules that inhibit disease-relevant proteins represents a longstanding challenge of medicinal chemistry. Here, we describe an approach for encoding this challenge—the inhibition of a human drug target—into a microbial host and using it to guide the discovery and biosynthesis of targeted, biologically active natural products. This approach identified two previously unknown terpenoid inhibitors of protein tyrosine phosphatase 1B (PTP1B), an elusive therapeutic target for the treatment of diabetes and cancer. Both inhibitors appear to target an allosteric site, which confers selectivity, and can inhibit PTP1B in living cells. A screen of 24 uncharacterized terpene synthases from a pool of 4,464 genes uncovered additional hits, demonstrating a scalable discovery approach, and the incorporation of different PTPs into the microbial host yielded alternative PTP-specific detection systems. Findings illustrate the potential for using microbes to discover and build natural products that exhibit precisely defined biochemical activities yet possess unanticipated structures and/or binding sites.

Metal-oxide interfaces provide a new opportunity to improve catalytic activity based on electronic and chemical interactions at the interface. Constructing high density of interfaces is essential in maximizing synergistic interactions. Here, we demonstrate that Cu/ceria interfaces made by sintering nanocrystals facilitate C-C coupling reactions in electrochemical reduction of CO2. The Cu/ceria catalyst enhances the selectivity of ethylene and ethanol production with suppressing H2 evolution in comparison with Cu catalysts. The intrinsic activity for ethylene production is enhanced by decreasing the atomic ratio of Cu/Ce, revealing the Cu atoms near ceria are an active site for C-C coupling reactions. The ceria is proposed to weaken hydrogen binding energy of adjacent Cu sites and stabilize an *OCCO intermediate via an additional chemical interaction with an oxygen atom of the *OCCO. This work offers new insights into the role of the metal-oxide interface in the electrochemical reduction of CO2 to high-value chemicals.