Yong-Sok Lee
NIH, CIT, CMM
Bldg 12A, Room 2049
12 South Drive MSC 5624
Bethesda, MD 20892-5624
leeys@mail.nih.gov

I carry out computer simulations at the level of quantum mechanics and molecular mechanics to investigate the reaction mechanism of small molecules, protein-ligand interaction, and enzyme mechanism with the aim of drug discovery. My research interest also includes proton transfer process in both proteins and nanotubes. A brief description of my work is as follows:

Design and Synthesis of Bioactive Compounds

Based on the structures of inhibitors/agonists/anatgonists and their experimental data (e.g., IC50 and Ki), I develop pharmacophore requirements for bio-active compounds to facilitate the discovery of novel compounds for the treatments of diseases. Examples are opioid analgegics, cannabinoid antagonists, transporter protein (TSPO) ligands (e.g., PK11195 and benzodiazepine) for brain imaging, and radiopharmaceticals for tumor imaging (tetrahydroxamate chelators of Zirconium89) as well as for alpha-immunotherapy (At211 labeled antibody).

Enzyme Mechanism

Utilizing hybrid potentials of quantum mechanics (GAMESS) and molecular mechanics (CHARMM), I investigate enzyme mechanism (e.g., aldose reductase, chorismate mutase and adenynyl cyclase). This study not only allows one to map the reaction pathway catalyzed by enzymes but also to ascertain the transition state geometry of a substrate, which in turn can be used for designing transition state analogs that tightly bind to a protein of interest.

Proton Transfer Process

Proton transfer is one of the most fundamental processes in biology and chemistry. In order to gain insight into the mechanism of proton transfer process, we carry out ab-intio quantum chemical molecular dynamics simulations on proteins (e.g., bacteriorhodopsin) and carbon nanotubes. This work does address the question such as energy barrier for proton hopping via a hydrogen-bonded water chain.

Selected Publications