John O. Trent, PhD

Research Program
Structural Biology

Education

B.Sc., University of Canterbury, New Zealand, Chemistry, 1988
Ph.D., University of Canterbury, New Zealand, Chemistry, 1992
Postdoc, University of Geneva, Switzerland, Organic Chemistry, 1992-1994

Research and Professional Experience
1994-1996
Postdoctoral Fellowship/Lecturer, CRC Biomolecular Structure Unit, The Institute of Cancer Research, Sutton, Surrey, UK.

1996-1997
Scientific Staff/Lecturer, CRC Biomolecular Structure Unit, The Institute of Cancer Research, Sutton, Surrey, UK.

1997-1999
Research Assistant Professor, Division of Hematology/Oncology, University of Alabama, Birmingham; and Associate Scientist, Comprehensive Cancer Center, University of Alabama

1998-present
Director, Birmingham Veterans Administration Molecular Modeling Shared Facility

1999-present
Assistant Professor, Division of Internal Medicine, Department of Medicine, University of Louisville, KY

1999-present
Associate Scientist, James Graham Brown Cancer Center, University of Louisville

1999-present
Director, James Graham Brown Cancer Center Molecular Modeling Facility, University of Louisville

2000-present
Assistant Professor of Biochemistry & Molecular Biology and Chemistry, University of Louisville

2005-present
Associate Professor of Medicine, University of Louisville

Selected Awards and Professional Honors
1984-1987
Sir James Gear Scholarship

1988
Sir Neil Issac Scholarship

1988-1991
University Grants Committee Post-Graduate Scholarship

1989
Winner, New Zealand Institute of Chemistry Conference Student Paper Competition

1990, 1991
Rochester and Rutherford Scholarship

1991
Judge for the New Zealand Institute of Chemistry Conference Student Paper Competition

Research Interest

Structure-based drug design, macromolecular molecular dynamics modeling of proteins, DNA and RNA drug discovery.

My group uses numerous computational techniques to complement experimental approaches aimed at understanding macromolecular interactions. The methods include molecular dynamics, free energy perturbation calculations, and Monte-Carlo methods as applied to real world problems. The combination of modeling techniques with different experimental modalities such as NMR, X-ray diffraction and thermodynamic methods is synergistic, and is the key to understanding structure and function. We have successfully modeled the structure of the nucleolin binding quadruplex, as verified by biophysical studies such as CD (with P. Bates), analytical ultracentrifugation and NMR (with A. Lane). We also have produced detailed rhodopsin-based homology models of the CCR5 and CXCR4 chemokine receptors, embedded in a complete, solvated lipid bilayer, that successfully account for the saturation mutation data obtained by Dr. S. C. Peiper at the Brown Cancer Center (now at Georgia Medical College, Augusta). We have a strong interest in quadruplex structure and as a drug target and collaborate with Dr. J. B. Chaires on the biophysical aspect of this work.

We also have enhanced our drug discovery program by establishing a distributing computing Grid for virtual screening. The Grid development is in collaboration with Dataseam and uses thousands of computer processors in schools across the Commonwealth of Kentucky. It is now routine in my laboratory to screen millions of potential compounds against a cancer target in days. We have successfully screened over 20 cancer targets that are moving into the laboratories for anticancer activity testing.

Publications