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 ab-initio quantum chemistry and molecular mechanics to better undersand the structure and function of bio-active compounds at the atomic level. My research interests include protein-ligand interaction, enzyme mechanism, and drug design as well as proton transfer process in both proteins and nanotubes. A brief description of my work is as follows:

Protein-Ligand Interaction

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 provide a structural basis for their observed experimental data. Examples are geldanamycin, an anti-cancer compound, for Heat Shock Protein 90 (HSP90), opioid analgegics, benzodiazepines, and positron emission tomography (PET) ligands for imaging.

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