Linda Jen-Jacobson

Address:
Department of Biological Sciences
University of Pittsburgh
320 Clapp Hall
4249 Fifth Avenue
Pittsburgh, PA 15260

Phone: 412-624-4969
Fax: 412-624-4759
Email: LJEN@pitt.edu
Homepage: Visit

Background:

When and where you received your PhD
University of Illinois, Champaign-Urbana, Illinois, 1967

Research:

Our research objective is to gain insight into the molecular determinants for high DNA site selectivity by proteins. We use the conceptual and analytical methods of biophysics and structural biochemistry in combination with the manipulation methods of synthetic chemistry and of molecular genetics. We are currently combining high resolution "structural-perturbation" methods with isothermal titration calorimetry to obtain complete thermodynamic profiles (i.e., changes in enthalpy, entropy, heat capacity); for protein-DNA complex formation, together with computational modeling to complement our interpretations. Some of our current work focuses on the thermodynamic consequences of molecular strain, experimental measurement of solvation changes upon binding, and the molecular properties of mutant proteins with reduced specificity. Our work points to the importance of time-dependent (dynamic); characteristics of protein-DNA complexes, including binding-dependent conformational transitions in the proteins and DNA and conformational-vibrational fluctuations in the protein-DNA complexes, so we are pursuing spectroscopic methods (NMR and ESR); that inform us about these dynamics. A profound understanding of these basic physicochemical principles and their applications is what we will ultimately need to develop methods for knowledge-based drug design and design of macromolecules to fulfill specific biological functions.