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

Enzyme Mechanism

Utilizing hybrid potentials of quantum mechanics (GAMESS) and moleculat mechanics (CHARMM), I study enzyme mechanism at the atomic level (e.g., aldose reductase, chorismate mutase and adenynyl cyclase). This study not only allows one to map the reaction pathway catalyzedby 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.

Protein-Ligand Interaction

Based on the structures of inhibitors and their experimental data (e.g., IC50), I develop pharmacophore requirements for inhibitors to provide a structural basis for observed experimental data. I also study the binding modes of inhibitors/substrates to proteins utilizing ab-intio quantum chemistry. An example includes the trans-cis isomerization of geldanamycin, an anti-cancer compound, catalyzed by Heat Shock Protein 90 (HSP90).

Proton Transfer Process

Proton transfer is one of the most important 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.

Enzyme Mechanism and Proton Transfer Process

Hassan SA, Hummer G and Lee YS: Effects of Electric Fields on Proton Transport through Water Chains. (2006) J. Chem. Phys. 124, 204510.

Lee YS and Krauss M: Dynamics of Proton Transfer in Bacteriorhodopsin. (2004) J. Am. Chem. Soc. 126, 2225-2230.

Lee YS and Krauss M: Structure and Reaction in the Active Site of Mammalian Adenylyl Cyclase . (2004) J. Phys. Chem. B. 108, 4508-4515.

Woodcock HL, Hodoscek M, Sherwood P, Lee YS, Schafer III HF and Brooks BR: Exploring the QM/MM Replica Method: A pathway optimization of the chorismate to prephenate Claisen Rearrangement Catalyzed by Chorismate Mutase. (2003) Theor. Chem. Acc. 109, 140-148.

Lee YS, Worthington SE, Krauss M and Brooks BR: Reaction Mechansim of Chorismate Mutase Studied by the Comibined Potentials of Quantum Mechanics and Molecular Mechanics. (2002) J. Phys. Chem. B 106, 12059-12065.

Lee YS, Hodoscek M, Brooks B and Kador PF: Catalytic Mechanism of Aldose Reductase Studied by the Combined Potentials of Quantum Mechanics and Molecular Mechanics. (1998) Biophys. Chem. 274, 27642-27650.

Lee YS, Marcu MG and Neckers L: Quantum Chemical Calculations and Mutational Analysis Suggest Heat Shock Protein 90 Catalyzes Trans-Cis Isomerization of Geldanamycin. (2004) Chem. Biol. 11, 991-998.

Neckers L and Lee YS: The Rules of Attraction. (2003) Nature 106, 357-358.

Lee, YS, Hodoscek M., Kador PF and Sugiyama K: Hydrogen Bonding Interactions between Aldose Reductase Complexed with NADP(H) and Inhibitor Tolrestat Studied by Molecular Dynamics Simulations and Binding assay (2003) Chem-Biol Interact. 143, 307-316.

Sugiyama K, Chen Z, Lee YS and Kador PF: Isolation of a Non-covalent Aldose Reductase-Nucleotide-Inhibitor Complex. (2000) Biochem. Pharmacol. 59, 329-336.

Lee YS, Sugiyama K and Kador PF: Rotamers of Tolrestat and Their Binding Mode to Aldose Reductase. (1999) Adv. Exp. Med. Biol. 463, 465-472.

Lee YS, Chen Z and Kador PF: Molecular Modeling Studies of the Binding Modes of Aldose Reductase Inhibitors at the Active Site of Human Aldose Reductase. (1998) Bioorg. Med. Chem. 6, 1811-1820.

Lee YS, Pearlstein R and Kador PF: Molecular Modeling Studies of Aldose Reductase Inhibitors. (1994) J. Med. Chem. 37, 787-792.

Hong SY, Kertesz M, Lee YS and Kim OK: Geometrical and Electronic Structures of Benzimidazobenzophenanthroline-Type Ladder Polymer (BBL) (1992) Macromolecules 25, 5424-5429.

Lee YS, Kertesz M and Elsenbaumer RL: The Importance of Energetics in the Design and Synthesis of Small Band Gap Conducting Polymer (1990) Chem. Mater. 2, 526-530.

Kindle JR, Bartoli FJ, Hoffman CA, Kim OK, Lee YS, Shirk JS and Kafafi ZH: Nonlinear Optical Properties of Heteroaromatic Ladder Polymers, BBL and BBB at 1.064 um . (1990) Appl. Phys. Lett. 56, 712-717.

Lee YS, Sharon DG, McNichol J and Silvers SJ: The Observation of CS2 Continuum-Like Emission Under Collision Free Conditions. (1989) Chem. Phys. Lett. 161, 116-121.

Kertesz M, Lee YS and Stewart JP: Structure and Electronic Structure of Polyacene . (1989) Int. J. Quantum Chem. 35, 305-312.

Lee YS and Kertesz M: The Effect of Heteroatomic Substitutions on the Band Gap of Polyacetylene and Polyparaphenylene Derivatives (1988) J. Chem. Phys. 88, 2609-2617.

Lee YS and Kertesz M: The Electronic Structure of Boron Carbide (BC3) (1988) J. Chem. Soc. Chem. Commun. 1, 75.

Lee YS and Kertesz M: The Effect of Additional Fused Rings on the Stabilities and the Band Gaps of Heteroconjugated Polymers (1987) Int. J. Quantum Chem. 21, 163-170.

Kertesz M and Lee YS: Energy Gap and Bond Length Alteration in Heterosubstituted Narrow Gap Semiconducting Polymers. (1987) J. Phys. Chem. 91, 2690-2692.