CURRICULUM VITAE
 

Name:                    Yi-der Chen

Business Address:   Mathematical Research Branch, National Institute of Diabetes and
                               Digestive and Kidney Diseases, National Institutes of Health,
                               Bethesda, MD 20892-2690.

Present Job Title:     Research Chemist
  
Phone Number:       301-496-5436 (phone)
                               301-402-0535 (fax)
  
Date of Birth:           May 29,1940.

Marital Status:         Married with two children.

Education and Degree:      
                  
                   B.S., National Taiwan University, Taipei, Taiwan. Chemical Engineering (1963).
                   M.S., National Tsing Hua University, Hsin Chu, Taiwan. Chemistry (1965).
                   Ph.D., Pennsylvania State University, University Park, Pa. Chemistry (1969)

Professional  Experience:                
                   Research Chemist,  Mathematical Research Branch, NIDDK,
                                                 National Institutes of Health, Sept., 1997-present.
                   Visiting Professor,   Department of Biochemistry, The Hong Kong University
                                                 of Science and Technology,  May-July, 1993, May 1995.
                   Research Chemist,  Laboratory of Molecular Biology, NIDDK,  National Institutes
                                                 of Health, July 1978- Sept. 1997.
                   Visiting Scientist,     Laboratory of Molecular Biology, NIDDK, National Institutes
                                                 of Health, 1972-1978.
                    Research Chemist, Division of Natural Sciences, University of California
                                                 at Santa Cruz, 1969-1972.



General Research Interests:  

(1). Free Energy Transduction in Biology: Active Transport Across Membranes, Fluctuation Induced Active Transport, Directional Movement of Brownian Particles in a Fluctuating Potential Field, Kinesin Movement on Microtubule, Muscle Contraction, Flagella Motor Rotation.
                 
(2). Theoretical Modeling and Application of Statistical Mechanics and Thermodynamics in Biology:  Equilibrium and Kinetic Studies of Binding of One or More Ligands to Linear Biopolymers, Treadmilling and Phase Instability in Microtubule Aggregation, Theory of Noise and Fluctuation in Biological Systems, Theory of Protein Folding.



Current research projects:
  
(1). Theoretic formalism for kinesin motility: In this project, we formulate mathematical formalisms connecting the biochemical mechanisms of kinesin motors and the mechanical movement of the bead measured in a typical motility assay. The purpose is to provide a method to quantitatively assess or differentiate between various biochemical kinetic models for kinesin motors based on mechanical data measured in motility assays. In motility assays, it is the movement of the bead, not the movement of the kinesin, that is directly measured. Therefore, the mechanical data obtained in motility assays can not be directly used to elucidate the kinetic mechanism of kinesin movement on microtubule. We have finished the derivation of the formalism for the case that the kinesin motor used to move the bead in the motility assay is one-headed. Currently, we are extending the formulation to two-headed kinesins.

(2). Molecular dynamics simulations of kinesin molecules and kinesin-tubulin complexes: In this project, we investigate the molecular conformations of kinesin motors in different nucleotide states using “Molecular Dynamics Simulation” method. The purpose is to examine how the ATP hydrolysis reaction at the catalytic site of the motor is coupled to the translocation of the motor on the microtubule. That is, we are interested in the “molecular mechanism” of free energy transduction. It is obvious that the generation of force and the translocation of a kinesin motor on a mirotubule depend on the nucleotide state of the motor. How the information at the catalytic site is transmitted to the microtubule binding site and the “lever’ arm site is an interesting but difficult question. Molecular dynamics simulation is a useful tool to study the molecular basis of this information transmission. Simulations on kinesin motors in the absence of microtubule showed that both the motor core and the linker region (the lever arm) change their conformations according to the bound nucleotide. We are extending the study to including the microtubule in the simulation.

(3). Theoretical modeling on muscle contraction regulation: In this project, we carry out a theoretical calculation on the kinetics of binding myosin sub-fragment 1 to regulated actin for two different muscle regulation models:  the two-state Hill model ( Hill, Eisenberg, and Green, 1980. PNAS 77: 3186-90) and the three-state Geeves model (McKillop and Geeves, 1993, Biophys. J. 65:693-701). The purpose of this study is to examine whether the Hill model can account for kinetic binding data, specifically for the ‘lag’ found in the kinetic binding curves when excess S1 binds to regulated actin filaments in the absence of calcium. It had been claimed before that the two-state Hill model is unable to account for such a lag. Thus, an alternative three-state Geeves model was proposed and claimed to be essential for fitting the lag phase. Here we show that the Hill model can account for the lag in the kinetic binding data at least as well as the Geeves model. We further show that both models are indistinguishable in their ability/inability to account for existing kinetic and equilibrium binding data. Thus, the Hill model cannot be ruled out on the basis of existing kinetic and equilibrium binding data.