Mountains: Faith and Hope

Dale E. Tronrud
Member of the P. Andrew Karplus lab
Department of Biochemistry and Biophysics
Oregon State University
Corvallis, OR, 97331, USA
det101@daletronrud.com

X-ray crystallography is a technique where a crystal of a material is illuminated by a beam of x-rays.  The scattering of those x-rays are measured and used to determine the arrangement of atoms in that crystal.  The methods for determining the structure of large molecules, such as proteins and DNA, are of particular interest to me.  I have developed a number of novel methods, written papers describing them, and incorporated these ideas into the TNT refinement package.  Unfortunately quite a few of my ideas have been implemented in TNT without ever having been written up in papers.  It’s my own fault, of course…

 

I have worked on a number of crystal structures myself.  Not many, but they are good ones.  Using data collected by Roger Fenna and Mike Schmid, I refined a model for the FMO protein from the Green Sulfur Bacteria formerly known as Prosthecochloris aestuarii 2K.  This 1.9Å model stood as the highest resolution model of a chlorophyll containing protein until 2004.  In 2009 I published and deposited a 1.3Å model of this same protein (PDB code: 3EOJ) and regained the title of highest resolution chlorophyll containing protein.

 

Since none of the refinement programs available in the 1980’s could handle the complexities of a bacteriochlorophyll-a molecule I needed to use Lynn Ten Eyck’s TNT refinement program, which is how I got into that business.

 

I have also worked on a number of inhibitor complexes with the endopeptidase Thermolysin. Thermolysin was a great system to work with because one could soak in rather large inhibitors (the equivalent of four amino acids in size).  We worked with a variety of inhibitors to probe various ideas for the design of better inhibitors, and by analogy, better drugs.

 

While I had been working in Brian Matthews’ lab for many years, that lab shut down last year.  I’m currently working for Andy Karplus at Oregon State University. The main thrust of my work there is the exploration of the practical consequences of using his new library of standard values for bond lengths and angles in the peptide backbone.

TNT

TNT is a package of programs used to optimize the fit of a model of a protein/nucleic acid to X-ray diffraction data while maintaining quality bond lengths, angles, and other good things.

Method Papers

Structure Papers

  • (pdf) Structural Analysis of the Inhibition of Thermolysin by an Active-Site-Directed Irreversible Inhibitor, Holmes, M.A., Tronrud, D.E. and Matthews, B.W., Biochemistry, 22, 236-240 (1983) (I performed the refinement of this inhibitor using the earliest version of TNT.  The program to produce Fig 4 was the first program I wrote in the lab.)
  • (pdf) Structure and x-ray amino acid sequence of a bacteriochlorophyll a protein from prosthecochloris aestuarii refined at 1.9Å resolution, Tronrud, D.E., Schmid, M.F. and Matthews, B.W., J. Mol. Biol. 188, 443-454 (1986).
  • (pdf) Slow- and fast-binding inhibitors of thermolysin display different modes of binding – Crystallographic analysis of extended phosphonamidate transition-state analogues, Holden, H.M., Tronrud, D.E., Monzingo, A.F., Weaver, L.H. and Matthews, B.W., Biochemistry, 26, 8542-8553 (1987) (Art collected the data and began the refinement of ZGPLL while Hazel and I worked together to collect the data for ZFPLA and finish the refinement of both inhibitors.)
  • (---) Structures of two thermolysin-inhibitor complexes that differ by a single hydrogen bond, Tronrud, D.E., Holden, H.M. and Matthews, B.W., Science, 235, 571-574 (1987) (Hazel and I worked together closely on these two inhibitors.)
  • (pdf) Analysis of the Effectiveness of Proline Substitutions and Glycine Replacements in Increase the Stability of Phage T4 Lysozyme, Nicholson, H., Tronrud, D.E., Becktel, W.J. and Matthews, B.W., Biopolymers, 32, 1431-1441 (1992) (My only contribution to this paper is the survey of phi-psi angles of proline and pre-proline residues.)
  • (pdf) Refinement of the Structure of a Water-Soluble Antenna Complex from Green Photosynthetic Bacteria by Incorporation of the Chemically Determined Amino Acid Sequence, Tronrud, D.E. and Matthews, B.W., in The Photosynthetic Reaction Center, Volume 1, 13-21 (1993)
  • (---) Refined structure of Cro repressor protein from bacteriophage λ suggests both flexibility and plasticity, Ohlendorf, D.H., Tronrud, D.E. and Matthews, B.W.,  J. Mol. Biol. 280, 129-136, (1998) (I completed the refinement of this structure.)
  • (---) The Structural Basis for the Difference in Absorbance Spectra for the FMO Antenna Protein from Various Green Sulfur Bacteria, Tronrud, D.E., Wen, J., Gay, L. and Blankenship, R.E., Photosyn. Res. 100(2), 79-87, (2009)

 

PhD Thesis

·        (pdf) The Refinement of Macromolecular Structures, Tronrud, D.E. (1986) (12MB, you didn’t expect it to be small, did you?)

PowerPoint Presentations

Copyright 2009 by Dale E. Tronrud.