Dickerson, Richard E.
Short Bio
Dickerson received a bachelor’s degree in chemistry from the Carnegie Institute of Technology in Pittsburgh (now Carnegie Mellon University) in 1953. Moving to the University of Minnesota, he earned a Ph.D. in physical chemistry in 1957, studying the structures of boron hydrides under the direction of Professor William N. Lipscomb. During two post-doctoral fellowships, first at Leeds University and then at Cambridge University, he helped to develop computational methods that paved the way for modern-day macromolecular crystallography. In the laboratory of John Kendrew at Cambridge, Dickerson along with Bror Strandberg, David Davies and David Phillips solved the first high-resolution x-ray crystal structure of a protein, myoglobin.
Biography
Dickerson began his academic career in 1959 as an assistant professor of physical chemistry at the University of Illinois. In 1963 he moved to the California Institute of Technology where he spent 18 years as an associate professor and then professor of physical chemistry. During this time, his analyses of the structures of cytochromes c from mammals, fish and bacteria allowed him to demonstrate the principles of evolution at the molecular level. As a consequence, he served as an expert witness in trials challenging the imposition of creationism on our science curricula, and lectured on the threat of creationism to science teaching.
In 1981 Dickerson moved from Caltech to UCLA with a joint appointment in the Division of Chemistry and Biochemistry and the Institute of Geophysics and Planetary Physics, the latter a consequence of his evolution vs. creationism interests. Dickerson was the first to carry out a single-crystal structure analysis of B-DNA, with what has become known as the “Dickerson dodecamer”: C-G-C-G-A-A-T-T-C-G-C-G. At UCLA he has continued his investigations of the structures of A- and B-DNA, and of complexes between DNA and drugs or proteins. He was elected to the National Academy of Sciences and American Academy of Arts and Sciences in 1985. During the academic year 1997-1998, Dickerson was the Newton-Abraham Visiting Professor in Medical, Biological and Chemical Science at Lincoln College and the Laboratory of Molecular Biophysics at Oxford University.
Dickerson is the author or co-author of 200 scientific papers and seven textbooks, various ones of which have been translated into eight languages. He resides in Pasadena, California with Lola, his wife of 45 years. They have five grown children and six grandchildren. Science has always been his primary hobby, but secondary ones have included mountain walking, opera, history, fine typography and antique typewriters and calculating machines.
Research Interest
We use X-ray crystal structure analysis to study the way that base sequence affects the local structure and deformability of the DNA double helix, in a manner that can be recognized by antitumor drugs and by DNA-binding proteins such as repressors, other control proteins, restriction enzymes, and the reverse transcriptase (RT) of HIV. We have found that the sequence G-G-C-C has a persistent bend under quite varied crystal condition, and believe it to be an important player when DNA wraps around a repressor or the histone core of nucleosomes. Other sequences of DNA 10-mers are being sequenced and solved to look for additional structure elements. What we learn is being applied to the design of minor groove binding antitumor drugs based on netropsin, distamycin, and anthramycin.
The Hin recombinase acts as a control element in Salmonella by inverting a 1 kb section of DNA, assisted by the Fis enhancer-binding protein. Fis is unique among DNA-binding proteins in that it binds specifically to more than 20 different sequences, of no obvious consensus. We have solved the structure of the Fis protein alone, and of the DNA-binding domain of Hin when complexed to its DNA site. We want to examine the structures of the entire Hin protein bound to DNA, and also the structures of Fis complexed with several of its binding sites, in order to understand how this complex recognition process takes place.
We have found that some drugs that bind to the minor groove of DNA inhibit strand synthesis by HIV RT, hence blocking incorporation of the AIDS provirus into the human genome. This inhibition is being investigated both structurally and kinetically, and we are looking for drugs whose inhibition of RT falls in a pharmaceutically useful range.
The familiar 2nd order fractal image of Benoit Mandelbrot is produced by iterating the expression: z’ = z2 + c. Iteration can be expanded to include higher powers of z, power series, and trigonometric and logarithmic functions, in the more general expression: z’ = a *f(z)*g(z) + c = a *F(z) + c, where f(z), g(z) and F(z) are functions of z and a is a constant. For F(z) = zn , a is no more than a scale constant governing the size of the fractal image. With increasing a , the image shrinks according to the scale product equation: a *W a n-1 = constant, where Wa is a measure of image width. Higher order zn Mandelbrot figures shrink less rapidly than does z2 . But for power series as simple as z2 + z3 , or for higher mathematical functions, a is critical in determining the shape of the resultant fractal image. For a power series the fractal image at low values of a is that which would be observed using only the highest term of the series. In contrast, at sufficiently high a values the image is that which would be obtained using only the lowest power term. Hence iteration of the function F(z) = z2 + z3 + z5 yields an ideal fifth-order Mandelbrot figure at low a and the familiar second-order figure at high a .
If a mathematical function can be expressed as a power series, then its behavior in the limit of large a values is identical to that obtained by using only the first or lowest-power term of the series, which can be defined as the reduced function. The reduced function for sin(z) is +z, and that for [1 – cos(z)] is +z2 /2. Hence at sufficiently high a , the result of iterating F(z) = sin(z)*[1 – cos(z)] is the same as that for F(z) = +z3 /2.