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 link above.
|
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.
Recent Publications (from "about us/papers" in the kinemage web site)
2013Richardson
(714KB)
|
"The Zen of model anomalies – Correct most of them. Treasure the meaningful valid few. Live serenely with the rest."
Richardson JS and Richardson DC (2013) In Advancing Methods in Biomolecular Crystallography, ed Read RJ, NATO conference volume from 2012 Erice crystallography school, Springer, in press (publ April 2013) doi: 10.1007/978-94-007-6232-9 |
2013Adams
(1.5MB)
|
"Advances, interactions, and future developments in the CNS, Phenix, and Rosetta structural biology software systems"
Adams PD, Baker D, Brunger AT, Das R, DiMaio F, Read RJ, Richardson JS, Terwilliger TC (2013) Ann. Rev. Biophys. 42 in press: doi: 10.1146/annurev-biophys-083012-130253 |
2013Richardson
(2.9MB)
|
"Doing molecular biophysics: Finding, naming, and picturing signal within complexity"
Richardson JS and Richardson DC (2013) Ann. Rev. Biophys. 42 in press: doi: 10.1146/annurev-biophys-083012-130353 |
2013Gainza
(350KB)
|
"OSPREY: Protein Design with Ensembles, Flexibility, and Provable Algorithms"
Gainza P, Roberts KE, Georgiev I, Lilien RH, Keedy DA, Chen C-Y, Reza F, Anderson AC, Richardson DC, Richardson JS and Donald BR (2013) Meth Enzymol 523:87-107 doi: 10.1016/B978-0-12-394292-0.00005-9 |
2013Leaver-Fay
(3MB)
SuppData |
"Scientific benchmarks for updating the Rosetta energy function"
Leaver-Fay A, O'Meara MJ, Tyka M, Jacak R, Song Y, Kellogg EH, Thompson J, Davis IW, Pache RA, Lyskov S, Gray JJ, Kortemme T, Richardson JS, Havranek JJ, Snoeyink J, Baker D, Kuhlman B (2013) Meth Enzymol 523109-143 doi: 10.1016/B978-0-12-394292-0.00006-0 |
2013Richardson
(2MB) |
""The Plot" Thickens: More Data, More Dimensions, More Uses"
Richardson JS, Keedy DK, & Richardson DC (2013) Book Chapter: ISBN: 978-981-4449-15-1 (ebook) |
2012Richardson
(2MB) |
"Studying and Polishing the PDB’s Macromolecules"
Richardson JS & Richardson DC (2012) Biopolymers 99(3)170-182. doi: 10.1002/bip.22108 |
2012Keedy
(576 KB) |
"The Role of Local Backrub Motions in Evolved and Designed Mutations."
Keedy DA, Georgiev I, Triplett EB, Donald BR, Richardson DC, & Richardson JS (2012) PLoS Comp Biol 8(8). doi: 10.1371/journal.pcbi.1002629 (open access) |
2012Echols
(750KBMB) |
"
Graphical tools for macromolecular crystallography in PHENIX"
Echols N, Grosse-Kunstleve RW, Afonine PV, Bunko ́czi G, Chen VB, Headd JJ, McCoy AJ, Moriarty NW, Read RJ, Richardson DC, Richardson JS, Terwilliger TC, & Adams PD (2012) J. Appl. Cryst. 45:581-586. doi:10.1107/S0021889812017293 (open access) |
2012Headd
(1.1MB) |
"Use of knowledge-based restraints in phenix.refine to improve macromolecular refinement at low resolution"
Headd JJ, Echols N, Afonine PV, Grosse-Kunstleve RW, Chen VB, Moriarty NW, Richardson DC, Richardson JS, & Adams PD (2012) Acta Cryst D68:381-390. doi: 10.1107/S0907444911047834 (open access) |
2011Read
(2.2MB) |
"A New Generation of Crystallographic Validation Tools for the Protein Data Bank"
Read RJ, Adams PD, Arendall WB, Brunger AT, Emsley P, Joosten RP, Kleywegt GJ, Krissinel EB, Lütteke T, Otwinowski Z, Perrakis A, Richardson JS, Sheffler WH, Smith JL, Tickle IJ, Vriend G, & Zwart PH (2011) Structure 19:1395-1412. doi: 10.1016/j.str.2011.08.006 (open access) |
2011Adams
(2.2MB) |
"The Phenix software for automated determination of macromolecular structures"
Adams PD, Afonine PV, Bunkóczi G, Chen VB, Echols N, Headd JJ, Hung L-W, Jain S, Kapral GJ, Grosse-Kunstleve RW, McCoy AJ, Moriarty NW, Oeffner RD, Read RJ, Richardson DC, Richardson JS, Terwilliger TC, Zwart PH (2011) Methods 55:94-106. doi: 10.1016/j.ymeth.2011.07.005 |
2011Dunkle
(2.2MB) |
"Structures of the Bacterial Ribosome in Classical and Hybrid States of tRNA Binding"
Dunkle JA, Wang L, Feldman MB, Pulk A, Chen VB, Kapral GJ, Noeske J, Richardson JS, Blanchard SC, & Doudna Cate JH (2011) Science 332:981-984. doi: 10.1126/science.1202692 |
2011Tyka
(2.2MB)
SuppData |
"Alternate States of Proteins Revealed by Detailed Energy Landscape Mapping"
Tyka MD, Keedy DA, André I, DiMaio F, Song Y, Richardson DC, Richardson JS & David Baker D (2011) J Mol Biol 405(2):607-618. doi: /10.1016/j.jmb.2010.11.008 (open access) |
2010Adams
(152KB) |
"PHENIX: a comprehensive Python-based system for macromolecular structure solution"
Adams PD, Afonine PV, Bunkóczi G, Chen VB, Davis IW, Echols N, Headd JJ, Hung L-W, Kapral GJ, Grosse-Kunstleve RW, McCoy AJ, Moriarty NW, Oeffner R, Read RJ, Richardson DC, Richardson JS, Terwilliger TC, Zwart PH (2010) Acta Cryst D66:213-221. doi: 10.1107/S0907444909052925 (open access) |
2010Chen
(1.6MB) |
"MolProbity: all-atom structure validation for macromolecular crystallography"
Chen VB, Arendall WB, Headd JJ, Keedy DA, Immormino RM, Kapral GJ, Murray LW, Richardson JS & Richardson DC (2010) Acta Cryst D66:12-21 doi: 10.1107/S0907444909042073 (open access) |
2009Adams
(205KB) |
"Recent developments in phasing and structure refinement for macromolecular crystallography"
Adams PD, Afonine PV, Grosse-Kunstleve RW, Read RJ, Richardson JS, Richardson DC & Terwilliger TC (2009) Current Opinion in Structural Biology 19:566-572 doi: 10.1016/j.sbi.2009.07.014 |
2009Chen
(643KB) |
"KiNG (Kinemage, Next Generation): A versatile interactive molecular and scientific visualization program"
Chen VB, Davis IW & Richardson DC (2009) Protein Sci 18:2403-2409 doi: 10.1002/pro.250 (open access) |
2009Keedy
(1.5MB)
SuppData |
"The other 90% of the protein: Assessment beyond the Cαs for CASP8 template-based and high-accuracy models"
Keedy DA, Williams CJ, Headd JJ, Arendall WB, Chen VB, Kapral GJ, Gillespie RA, Block JN, Zemla A, Richardson DC & Richardson JS (2009) Proteins: Struc Func Bioinf 77(Suppl 9):29-49 doi: 10.1002/prot.22551 |
2009Bourne
(2.7MB)
Book Link |
" The Impact of Local Accuracy In Protein and RNA Structures: Validation As an Active Tool"
Richardson JS & Richardson DC (2009) Chapter 15 in Structural Bioinformatics, 2nd Edition, ed. J. Gu and P. Bourne. Wiley (New York). |
2009Block
(1.1MB) |
"KinImmerse: Macromolecular VR for NMR ensembles"
Block JN, Zielinski DJ, Chen VB, Davis IW, Vinson EC, Brady R, Richardson JS & Richardson DC (2009) Source Code Biol Med 4:3. doi: 10.1186/1751-0473-4-3 (open access) |
2009Headd
(450KB)
SuppData |
"Autofix for backward-fit sidechains: using MolProbity and real-space refinement to put misfits in their place"
Headd JJ, Immormino RM, Keedy DA, Emsley P, Richardson DC & Richardson JS (2009) J Struc Func Genomics 10:83-93. doi: 10.1007/s10969-008-9045-8 (open access) |
2008Georgiev
(488KB) |
"Algorithm for backrub motions in protein design"
Georgiev I, Keedy DA, Richardson JS, Richardson DC & Donald BR (2008) Bioinformatics 24:i196-i204. doi: 10.1093/bioinformatics/btn169 (open access) |
2008ROC
(1.1MB)
SuppData |
"RNA Backbone: Consensus All-angle Conformers and Modular String Nomenclature (an RNA Ontology Consortium contribution)"
Richardson JS, Schneider B, Murray LW, Kapral GJ, Immormino RM, Headd JJ, Richardson DC, Ham D, Hershkovits E, Williams LD, Keating KS, Pyle AM, David Micallef d, Westbrook J & Berman HM (2008) RNA 14 :465-481. doi: 10.1261/rna.657708 (open access) |
2008Wang
(868KB) |
"RNABC: forward kinematics to reduce all-atom steric clashes in RNA backbone"
Wang X, Kapral GJ, Murray LW, Richardson DC, Richardson JS & Snoeyink J (2008) J Math Biol 56:253-278. doi: 10.1007/s00285-007-0082 |
2007Davis
(2.2MB) |
"MolProbity: all-atom contacts and structure validation for proteins and nucleic acids"
Davis IW, Leaver-Fay A, Chen VB, Block JN, Kapral GJ, Wang X, Murray LW, Arendall WB, Snoeyink J, Richardson JS & Richardson DC (2007) Nucleic Acids Res 35 W375-W383. doi:10.1093/nar/gkm216 (open access) |
2006Davis
(464KB)
SuppData &
hi-res img |
"The backrub motion: How protein backbone shrugs when a sidechain dances"
Davis IW, Arendall WB, Richardson DC, & Richardson JS (2006) Structure 14, 265-274. doi:10.1016/j.str.2005.10.007 (Supplementary data available also.) |
2006ROC
(596KB) |
"The RNA Ontology Consortium: An Open Invitation to the RNA Community"
Leontis NB, Altman R, Berman HM, Brenner SE, Brown J, Engelke D, Harvey SC, Holbrook SR, Jossinet F, Lewis SE, Major F, Mathews DH, Richardson JS, Williamson JR & Westhof E (2006) RNA 12, 533-541. doi:10.1261/rna.2343206 (open access) |
2005Arendall
(368KB)
Abstract |
"A test of enhancing model accuracy in high-throughput crystallography"
Arendall WB, Tempel W, Richardson JS, Zhou W, Wang S, Davis IW, Liu Z-J, Rose JP, Carson WM, Luo M, Richardson DC, & Wang B-C. (2005) J Struc Func Genomics 6, 1-11. doi:10.1007/s10969-005-3138-4 |
2004Davis
(668KB)
Abstract |
"MolProbity: structure validation and all-atom contact analysis for nucleic acids and their complexes"
Davis IW, Murray LW, Richardson JS, & Richardson DC. (2004) . Nucleic Acids Res 32 W615-619. doi:10.1093/nar/gkh398 (open access) |
2004Videau
(868KB)
Abstract |
"The Cis Pro Touch-Turn: A Rare Motif Preferred at Functional Sites"
Videau LL, Arendall WB, & Richardson JS. (2004) Proteins: Struc Func Bioinf 56, 298-309. doi:10.1002/prot.20101 |
2004Kapp
(480KB)
Abstract |
"Kinetic Role of Helix Caps in Protein Folding is Context-Dependent"
Kapp GT, Richardson JS, & Oas TG. (2004) Biochemistry 43, 3814-3823. doi:10.1021/bi035683k |
2003Murray
(620KB)
Abstract |
"RNA Backbone Is Rotameric"
Murray LW, Arendall WB, Richardson DC, & Richardson JS (2003) PNAS-USA 100, 13904-13909. doi:10.1073/pnas.1835769100 |
2003Lovell
(790KB)
Abstract |
"Structure Validation by Cα Geometry: φ,ψ and Cβ Deviation."
Lovell SC, Davis IW, Arendall WB, de Bakker PIW, Word JM, Prisant MG, Richardson JS, & Richardson DC (2003) Proteins: Struc Func Genet 50, 437-450. doi:10.1002/prot.10286 |
2003Methods
(780KB)
Abstract |
"New Tools and Data for Improving Structures, Using All-Atom Contacts. "
Richardson JS, Arendall WB, & Richardson DC (2003) Chapter in Methods in Enzymology: Macromolecular Crystallography, Part D, ed. C.W. Carter, Jr and R.M. Sweet. Academic Press (San Diego)374, 385-412. |
2002Richardson
(840KB)
Abstract |
"Natural β-Sheet Proteins Use Negative Design to Avoid Edge-to-Edge Aggregation."
Richardson JS & Richardson DC (2002) PNAS-USA 99, 2754-2759. doi:10.1073/pnas.052706099 |
2002BaMBEd
(2.2MB) |
"Teaching Molecular 3-D Literacy."
Richardson DC, Richardson JS (2002) Biochem Molec Biol Educ 30, 21-26. doi:10.1002/bmb.2002.494030010005 |
| 2001Volume F |
"MAGE, PROBE, and Kinemages."
Richardson DC & Richardson JS (2001) In International Tables for Crystallography, ed. Rossmann MG, Arnold E vol. F, chapter 25.2.8.,, 727-730 Kluwer Publ |
2000Lovell
(296KB)
Abstract |
"The Penultimate Rotamer Library."
Lovell SC, Word JM, Richardson JS, Richardson DC (2000) Proteins: Struc Func Genet 40, 389-408. doi: 10.1002/1097-0134(20000815)40:3<389::AID-PROT50>3.0.CO;2-2 |
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.
Lab Members (from "about us/contacts" in the kinemage web site)
|
|
| 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 |
| Jeff Headd |
Research Associate |
 |
jheadd AT gmail.com |
919-684-6010 |
| Lindsay Deis |
Grad Student |
 |
lindsay.deis AT duke.edu |
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 |
| Gary Kapral |
Grad Student |
 |
gary.kapral AT duke.edu |
919-681-8826 |
| 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 |
| Jo Anna Wiersma Capp |
Grad Student |
 |
jo.wiersma AT duke.edu |
919-684-6010 |
Past Lab Members |
| Name |
Currently |
Looked
Like |
e-mail |
|---|
| Vincent Chen |
Madison, Wisc. |
 |
vbchen AT gmail.com |
| Daniel Keedy |
Research Associate, Fraser Lab UCSF |
 |
daniel.keedy AT gmail.com |
| Jeremy Block |
advocate of responsible behavior |
 |
jeremy.block AT gmail.com |
| Ian Davis |
Grass Roots Biotechnology |
 |
ian.w.davis AT gmail.com |
| 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 |
| Laura Murray |
Research Associate | Pyle Laboratory (Yale) |
 |
gaultheria AT gmail.com |
| Xueyi Wang |
Assistant Professor
NW Nazarene U, Nampa,ID |
 |
xwang AT nnu dot edu |
| Michael Word |
Open Eye Software
Santa Fe, NM |
 |
word27605 AT gmail.com |
|
