Karl F. Freed Professor

Born Brooklyn, New York, 1942.
Columbia University, B.S., 1963.
Harvard University, A.M., 1965; Ph.D., 1967.
University of Manchester, England, NATO Postdoctoral Fellow, 1967-68.
The University of Chicago, Professor, 1968-.

Accolades

Fellow, American Academy of Arts and Sciences.
Fellow, American Physical Society.
1976 Faraday Division of the Royal Chemical Society and the American Chemical Society Award in Pure Chemistry.
1973 Marlow Medal.
1972-1977 Camille and Henry Dreyfus Teacher-Scholar Fellow.
1972-1973 Senior Visiting Fellowship, Cavendish Laboratory, Cambridge, England.
1972-1973 Guggenheim Fellow.
1969-1970 Dupont Faculty Fellow.
1969-1971 Alfred P. Sloan Fellow.

OFFICE: 929 E. 57th St., GCIS E 231, Chicago, IL 60637

PHONE: (773)702-7202

FAX: (773)702-5863

E-MAIL: freed@uchicago.edu

WEB: http://home.uchicago.edu/~freed

RESEARCH INTERESTS:

Our research include the statistical mechanics of polymers in the liquid phase, protein dynamics aggregation, and folding, equilibrium aggregation phenomena, and molecular electronic structure.


We have developed a theory for the statistical thermodynamics of polymers in the liquid state. Our analytical theory is the first and only one to describe the influence of monomer molecular structure on the thermodynamic properties of polymer mixtures. Several applications explain small angle neutron scattering and thermodynamic experiments for polymer mixtures. Our theoretical predictions of a strong pressure dependence to the small angle neutron scattering intensities has been verified. Likewise, we have predicted the possibility that certain block copolymers will form mesoscopically ordered self-assembled structures in the liquid phase upon heating, a bold prediction subsequently verified experimentally. Recent extensions of the theory consider random copolymers, the influence of short chain branching, monomer structure and chain semiflexibility on miscibilities of polymers in the liquid phase, as well as the phase behavior of liquid crystalline systems and the glass transition in polymer systems. The work on the glass transition is providing the first theoretical understanding for the molecular basis of glass fragiliity. Other theoretical work on polymers describes the common behavior exhibited by reversible equilibrium aggregating systems, including synthetic polymers and the proteins actin and tubulin. We have devised a density functional theory of interfaces in polymer systems to describe interfaces between phase separated polymers and surface segregation profiles of polymers near an impenetrable, patterned surface.


Flexible aqueous peptides and solution polymers have important dynamical processes on time scales far exceeding current capabilities for computer simulations. We have developed implicit solvent models that enormously reduce the computer time for simulating protein dynamics while reproducing the same dynamics as explicit solvent MD simulations for a small penta-peptide and for the folding of the 36 residue villin headpiece. This implicit solvent model has been used to study the folding dynamics of small peptides and the aggregation of beta-amyloid core fragments. Recent work compares the predictions of several widely used force fields for protein simulations, showing that the dispersion in their predictions far exceeds any errors in our implicit solvent model. The simulations show a residue specific dependence of conformational transitions in individual amino acid backbones. We have developed a mode-coupling theory for long time protein and polymer dynamics that extends the information from computer simulations to longer time scales. Our model for the unfolded state of proteins agrees well with data from NMR and small angle scattering experiments and simulatneously explains the propenisites with which each amino acid participates in secondary structures in folded proteins.


We have developed a highly correlated ab initio electronic structure method for the difficult problem of describing molecular electronic excited states. The method is a multi-configurational generalization of the widely used MPn single reference configuration methods that are available in many electronic structure packages. These ab initio methods have been applied to describe the excited states of a number of conjugated pi-electron systems, where our computed energies and oscillator strengths rival in accuracy the most advanced ab initio methods. Additional applications have been made to computing two-dimensional methyl mercaptan and 3-dimensional hydrogen sulfide potential energy surfaces for the electronic excited states that participate in non-adiabatic photodissociation experiments carried out by Professor Butler's group. (The computations have been performed by a theory-experiment student also working with Prof. Butler.) Other work is focused on computing electronic spectra of radicals in interstellar space and the properties of biological chromophores in a protein environment.


Our unique electronic structure methods enabled us to derive from first principles the true valence shell effective Hamiltonian that is mimicked by the model Hamiltonians of purely semiempirical molecular orbital theories of molecular electronic structure. We have computed the first fully correlated "ab initio" pi-electron Hamiltonian that demonstrates why some assumptions of semiempirical pi-electron theories are correct, but our computations for small conjugated pi-electron systems indicate deficiencies of these older methods along with theoretically justified methods for their improvement.


Selected References

Benchmarking Implicit Solvent Folding Simulations of the Amyloid ß(10-35) Fragment. A. Kent, A. K. Jha, J. E. Fitzgerald, and K. F. Freed, J. Phys. Chem. B 112, 6175—86 (2008).

Potential Energy Curve for Isomerization of N2H2 Using the Improved Virtual Orbital Multireference Möller-Plesset (MRPT) Perturbation Theory. R. K. Chaudhuri, K. F. Freed, S. K. Chattopadhyay, and U. K. S. Mahapatra, J. Chem. Phys. 128, 144304 (2008).

Influence of nonlinear electrostatics on transfer energies between liquid phases: Charge burial is far less expensive than Born model. H. Gong, G. M. Hocky, and K. F. Freed, Proc. Natl. Acad. Sci. (US) 105,11146 (2008).

Quantifying the Structural Requirements of the Folding Transition State of Protein A and Other Systems. M. C. Baxa, K. F. Freed, and T. R. Sosnick, J. Mol. Biol. 381, 1362 (2008).

Multi-step Relaxation in Equilibrium Polymer Solutions: A Minimal Model of Relaxation in  “Complex” Fluids. E. B. Stukalin, J. F. Douglas, and K. F. Freed, J. Chem. Phys. 129, 094901 (2008).

Competition between Self-assembly and Surface Adsorption. J. Dudowicz, J. F. Douglas, and K. F. Freed, J. Chem. Phys. 130, 084903 (2009).

ψ-Constrained Simulations of Protein Folding Transition States: Implications for calculating f. M. Baxa, K. F. Freed, and T. R. Sosnick, J. Mol. Biol. 386, 9920-8 (2009).

Langevin-Debye Model for Nonlinear Electrostatic Screening of Solvated Ion. H. Gong and K. F. Freed, Phys. Rev. Lett. 102, 057603 (2009). Also in February 15, 2009 issue of Virtual Journal of Biological Physics Research.

Extension of Lattice Cluster Theory to Strongly Interacting, Self-assembling Polymeric Systems. K. F. Freed, J. Chem. Phys. 130, 061103 (2009).

Mimicking the Folding Pathway to Improve Homology-free Protein Structure Prediction. J. DeBartolo, A.Colubri, A. Jha, J. E. Fitzgerald, K. F. Freed, and T. R. Sosnick, Proc. Natl. Acad. Sci. 106, 3734-9 (2009).

More publications are available at http://home.uchicago.edu/~freed/