Jane & Dave & Hal, Jr.

David C. Richardson

Professor of Biochemistry

Jane S. Richardson

James B. Duke Professor of Biochemistry


Contact Information

Telephone: (919) 684-6010

Fax: (919) 684-8885

e-mail dcrjsr AT kinemage.biochem.duke.edu

Mailing Address

Department of Biochemistry

132 Nanaline H. Duke

Box 3711, DUMC

Durham, NC 27710

Research Interests

Structural Bioinformatics

3D structure validation and improvement for protein and RNA

...see tanstaauws The Main Richardson Web Site kinemage.biochem.duke.edu

JavaMage

JavaMage is the earliest and simplest version of our interactive web graphics. The Java picture is a "kinemage" (kinetic image). To rotate in 3-D, drag slowly with the mouse. To identify a point, click on it; to measure a distance, click on each end point. To see the fuller implementation in KiNG, try the MolProbity web Server

Research Interests

The long-term goal of the Richardson lab is to contribute to a deeper understanding of the 3D structures of proteins, including their description, determinants, folding, evolution, and control. This has now been broadened to include RNA structures. Our approaches include structural bioinformatics, macromolecular crystallography, molecular graphics, analysis of structures, and methods development, currently focussed on the improvement of structural accuracy.

Following on two of the earliest protein crystallographic structures (Staphylococcal nuclease and Cu,ZN superoxide dismutase), our continuing analysis and comparison of protein structures then led to an early classification system, new overall folds (such as the Greek key beta barrel, and what is now called the SS beta cross), and description of many new small-scale features (such as right-handed crossovers, beta bulges, helix N-caps and C-caps, and cisPro touch-turns). We now also analyze structural motifs in RNA, including an all-angle definition of conformers for RNA backbone.

We develop methods for representing protein structure, most notably the hand drawings that popularized ribbon schematics and formed the basis for the present computer ribbon drawings. We develop software to fill what we see as unmet needs, most notably kinemages (molecular graphics optimized for the communication of specific ideas in 3D) and the associated Mage and KiNG display programs, free software on Mac, PC, and Linux, widely used for teaching and databases as well as for research. Mage and KiNG incorporate many functions for analyzing and rebuilding macromolecules, including the "Backrub" tool for making realistic local movements in protein backbone.

We were among the first groups to do protein de novo design and made designs in all 4 of the major tertiary-structure types, using complex, native-like sequences (e. g., betabellin, Felix, babarellin, and SScorin). We introduced the concept of negative design, and we first pointed out the general problem of the more-or-less molten nature of most fully de novo designs. In order to treat internal packing in quantitative detail, we developed an all-atom contact algorithm to quantify and visualize the geometric details of molecular interaction; it uses all explicit H atoms and a very small probe sphere to show those surface patches where atoms are within 0.5 Å of exact van der Waals contact. This method gives a sensitive description of packing quality within or between molecules, for use in protein or drug design, for understanding structural features and interactions, and for designing non-disruptive mutations. All-atom contact analysis, along with crystallographic B-factors, allowed us to construct much-improved libraries and data distributions for protein sidechain rotamers and Ramachandran phi,psi backbone angles. All of these validation analyses can be run interactively on the MolProbity web service, including optimized hydrogen addition and automated correction of "flipped" sidechain amide or histidine orientations.

All-atom steric clashes are a powerful and sensitive way of finding problems in molecular structures, and even of suggesting how to make corrections. As part of the SECSG structural genomics effort, we used MolProbity diagnosis along with rebuilding and refinement on 29 SECSG structures, producing modest improvements in traditional crystallographic measures (R, Rfree, geometry, real-space residual) and dramatic order-of-magnitude improvements in all-atom clashscore and rotamer and Ramachandran outliers. We are now working to extend applicability to RNA and to NMR structures, and, as part of the PHENIX software team, to further integrate and automate these techniques in crystallography. A long-term vision is to enable the determination of accurate models even from low-resolution data.

For more details, see our kinemage web site at http://kinemage.biochem.duke.edu/, where all our software is available free and open-source, as well as datasets and examples. There is a service called MolProbity where you can run our structure validation tools on an uploaded file of your own or one chosen from the PDB or NDB, and display the results directly on-line in KiNG.
For Recent Publications  see "about us/papers" in the kinemage web site)

Lab Members (from "about us/contacts" in the kinemage web site)

Current Lab Members
Past Lab Members

Name Position Cast of
Characters
e-mail Telephone
David Richardson Professor dcr AT kinemage.biochem.duke.edu 919-684-6010
Jane Richardson Professor jsr AT kinemage.biochem.duke.edu 919-684-6010
Bryan Arendall Senior Research Associate arendall AT duke.edu 919-681-8827
Steven Lewis Research Associate smlewi AT gmail.com 919-684-6010
Bradley Hintze Grad Student bradley.hintze AT duke.edu 919-684-2217
Swati Jain Grad Student (CBB) swati.jain AT duke.edu 919-684-2217
Michael Prisant Senior Research Scientist michael.prisant AT gmail.com
Lizbeth Videau Staff Assistant videau AT biochem.duke.edu 919-684-6010
Christopher Williams Grad Student christopher.j.williams AT duke.edu 919-684-6010

Past Lab Members

Name Currently Looked
Like
e-mail
Gary Kapral Research Associate, Hargrove lab gary.kapral AT duke.edu 919-681-8826
Jeff Headd Johnson&Johnson jheadd AT gmail.com
Jo Anna Wiersma Capp Grad Student jo.wiersma AT duke.edu
Lindsay Deis Grad Student, Oas lab lindsay.deis AT duke.edu 919-684-4363
Vincent Chen BMRB, Madison, Wisc. vbchen AT gmail.com
Daniel Keedy Research Associate, Fraser lab UCSF daniel.keedy AT gmail.com
Jeremy Block Baruch College, NYC jeremy.block AT gmail.com
Laura Murray Research Associate | Pyle lab Yale gaultheria AT gmail.com
Ian Davis Grass Roots Biotechnology ian.w.davis AT gmail.com
Xueyi Wang Assistant Professor
NW Nazarene U, Nampa,ID
xwang AT nnu dot edu
Bob Immormino Research Associate
UNC-Chapel Hill
immormino AT gmail.com
Thom LaBean Associate Professor
Materials Science & Engineering, NC State
thlabean AT ncsu.edu
Simon Lovell Faculty of Life Sciences
Univ of Manchester, UK
simon.lovell AT man.ac.uk
Michael Word Open Eye Software
Santa Fe, NM
word27605 AT gmail.com