Kevin Karplus's Lab group

This web page is for Kevin Karplus's group in protein-structure prediction (and, eventually, protein design). The page has not been fully created yet, so you'll probably find more interesting stuff on the members' home pages.

Spring 2008 individual meeting schedule

Unscheduled papers

• Bin Qian, Srivatsan Raman, Rhiju Das, Philip Bradley, Airlie J. McCoy, Randy J. Read, and David Baker.
  High-resolution structure prediction and the crystallographic phase problem
  Nature 450, 259-264 (8 November 2007)
  doi:10.1038/nature06249
• Aleksandar Poleksic and Mark Fienup
  Optimizing the size of the sequence profiles to increase the accuracy of protein sequence alignments generated by profile-profile algorithms
  Bioinformatics 2008 24: 1145-1153;
  doi:10.1093/bioinformatics/btn097
  http://bioinformatics.oxfordjournals.org/cgi/content/abstract/24/9/1145
• Mark P Styczynski, Kyle L Jensen, Isidore Rigoutsos, Gregory Stephanopoulos
  BLOSUM62 miscalculations improve search performance
  Nature Biotechnology 26, 274 - 275 (2008)
  doi:10.1038/nbt0308-274
  http://www.nature.com/nbt/journal/v26/n3/full/nbt0308-274.html
• Thomas P. Treynor, Christina L. Vizcarra, Daniel Nedelcu, and Stephen L. Mayo
  Computationally designed libraries of fluorescent proteins evaluated by preservation and diversity of function
  PNAS | January 2, 2007 | vol. 104 | no. 1 | 48-53
  http://www.pnas.org/cgi/content/full/104/1/48
• Jonathan W. Neidigh, R. Matthew Fesinmeyer & Niels H. Andersen
  Designing a 20-residue protein
  Nature Structural Biology 9, 425 - 430 (2002)
  http://www.nature.com/nsmb/journal/v9/n6/full/nsb798.html#B1
• A. Su and S. L. Mayo
  Coupling backbone flexibility and amino acid sequence selection in protein design
  Protein Science, Vol 6, Issue 8 1701-1707
• Vanita D. Sood and David Baker.
  Recapitulation and Design of Protein Binding Peptide Structures and Sequences.
  Journal of Molecular Biology Volume 357, Issue 3, 31 March 2006, Pages 917-927.
  doi:10.1016/j.jmb.2006.01.045
• Christopher T. Saunders and David Baker
  Recapitulation of Protein Family Divergence using Flexible Backbone Protein Design
  Journal of Molecular Biology Volume 346, Issue 2, 18 February 2005, Pages 631-644
  doi:10.1016/j.jmb.2004.11.062
• David R. Westhead, Timothy W.F. Slidel, Tomas P.J. Flores, and Janet M. Thornton.
  Protein structural topology: Automated analysis and diagrammatic representation.
  Protein Science (1999), 8: 897-904
  http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=45405
• Jane S. Richardson and David C. Richardson.
  Natural beta-sheet proteins use negative design to avoid edge-to-edge aggregation.
  PNAS 99(5):2754-2759, March 5, 2002.
  http://www.pnas.org/cgi/content/full/99/5/2754
• Yan, Y. and Moult, J.
  Protein family clustering for structural genomics
  Journal of Molecular Biology, 353, 744-759 (2005)
  doi:10.1016/j.jmb.2005.08.058
• Dalton et al.
  title?
  Bioinformatics 19(10):1298-9 (2005)
  doi:10.1093/bioinformatics/btg141
• Lee and Chirikjian.
  title?
  Biophys J 86(2):1105-1117, (2003).
  (correction published (2004). Biophys J 86(4):2634)
  DOI:?
• Walther, Springer, and Cohen
  Helix-helix packing angle preferences for finite helix axes.
  Proteins 33(4):457-459, (1998). doi:10.1002/(SICI)1097-0134(19981201)33:4<457::AID-PROT1>3.0.CO;2-L
  (This is the paper from after Walther and Bowie agreed that this would have been the most appropriate null model to use. Martin M. and Kevin are not sure that they are right in reporting the propensities---the null model has zero probability for some of their rarely observed results, which resulted in enormous propensity for rare states!)
• Walther, Eisenhaber, and Argos.
  title?
  J Mol Biol 255:536-553, (1996).
  DOI?
• Bowie.
  title?
  Nature Struct Biol 4:915-917, (1997).
  DOI?
• Pawel Smialowski, Antonio J. Martin-Galiano, Aleksandra Mikolajka, Tobias Girschick, Tad A. Holak, and Dmitrij Frishman.
  Protein solubility: sequence based prediction and experimental verification
  Bioinformatics 23: 2536-2542, (2007).
  http://bioinformatics.oxfordjournals.org/cgi/content/abstract/23/19/2536
• Schaffer, A.A., Aravind, L., Madden, T.L., Shavirin, S., Spouge, J.L., Wolf, Y.I., Koonin, E.V., Altschul, S.F.
  Improving the accuracy of PSI-BLAST protein database searches with composition-based statistics and other refinements.
  Nucleic Acids Research, 29, 14:2994-3005 (2001)
  http://nar.oxfordjournals.org/cgi/content/full/29/14/2994
• Yu, Y.K., Wootton, J.C., Altschul, S.F.
  The compositional adjustment of amino acid substitution matrices.
  Proceedings of the National Academy of Sciences, 100, 26:15688--15693 (2003).
  http://www.pnas.org/cgi/content/full/100/26/15688 doi:10.1073/pnas.2533904100
• Altschul, S.F., Wootton, J.C., Gertz, E.M., Agarwala, R., Morgulis, A., Schaffer, A.A., Yu, Y.K.
  Protein database searches using compositionally adjusted substitution matrices.
  FEBS Journal, 272, 20:5101-5109 (2005)
  http://www.blackwell-synergy.com/doi/abs/10.1111/j.1742-4658.2005.04945.x doi:10.1111/j.1742-4658.2005.04945.x
• Yu, Y.K., Altschul, S.F.
  The construction of amino acid substitution matrices for the comparison of proteins with non-standard compositions.
  Bioinformatics, 21, 7:902-911 (2005)
  http://bioinformatics.oxfordjournals.org/cgi/content/full/21/7/902 doi:10.1093/bioinformatics/bti070
• Yu, Y.K., Gertz, E.M., Agarwala, R., Schaffer, A.A., Altschul, S.F.
  Retrieval accuracy, statistical significance and compositional similarity in protein sequence database searches.
  Nucleic Acids Research, 34, 20:5966-5973 (2006)
  http://nar.oxfordjournals.org/cgi/content/full/34/20/5966 doi:10.1093/nar/gkl731
• Milana Frenkel-Morgenstern, Rachel Magid, Eran Eyal, and Shmuel Pietrokovski.
  Refining intra-protein contact prediction by graph analysis
  BMC Bioinformatics. 2007; 8(Suppl 5): S6.
  Published online 2007 May 24.
  doi:10.1186/1471-2105-8-S5-S6
• Michael J. Sweredoski, Kevin J. Donovan, Bao D. Nguyen, A.J. Shaka, and Pierre Baldi
  Minimizing the overlap problem in protein NMR: a computational framework for precision amino acid labeling
  Bioinformatics 2007 23: 2829-2835.
  http://bioinformatics.oxfordjournals.org/cgi/content/abstract/23/21/2829
• Hung-Pin Peng and An-Suei Yang.
  Modeling protein loops with knowledge-based prediction of sequence-structure alignment.
  Bioinformatics 2007 23: 2836-2842.
  http://bioinformatics.oxfordjournals.org/cgi/content/abstract/23/21/2836
• Frank DiMaio, Dmitry A. Kondrashov, Eduard Bitto, Ameet Soni, Craig A. Bingman, George N. Phillips, Jr, and Jude W. Shavlik.
  Creating protein models from electron-density maps using particle-filtering methods.
  Bioinformatics 2007 23: 2851-2858.
  http://bioinformatics.oxfordjournals.org/cgi/content/abstract/23/21/2851

Old schedules

Register for class

Current projects

• http://www.soe.ucsc.edu/classes/bme220/Spring07/projects.html.
• http://www.soe.ucsc.edu/classes/bme220/Winter06/projects.html.
• http://www.soe.ucsc.edu/classes/bme220/Spring05/projects.html.

Lab Members

Kevin Karplus

Professor of Biomolecular Engineering, head of lab, master programmer for undertaker, predict-2nd, estimate-dist, correlated-columns, and C++ library.

Richard Hughey

Professor of Computer Engineering, master programmer for SAM tool suite.

Dietlind Gerloff

Assistant Professor of Biomolecular Engineering, structure predictor

George Shackelford

bioinformatics grad student, contact prediction in proteins Participated in CASP7.

Grant Thiltgen

MS/Phd student in bioinformatics. Summer 2005-current. Working on testing new H-bond-based local-structure alphabet. Participated in CASP7.

Firas Khatib

PhD student (inherited from Carol Rohl's lab). Currently writing up work done with Carol on finding knots in protein conformations generated by Rosetta. Working on generalizing knot-finding to "poke-finding" (pokes are slip knots). Participated in CASP7.

Josue Samayoa

PhD student (inherited from Carol Rohl's lab). Finished MS thesis on using residual dipolar coupling data to aid in choosing alignments of tragets to templates. Working with Fitnat Yldiz on simple repeats and short proteins in Vibrio cholerae.

John Archie

Started as rotation student W07. Worked on including predicted burial, bys, and protein-block local structure alphabets into undertaker cost function. Getting into protein design.

Hyunsung John Kim

Started as a Masters student Spring 2008, after BME 220 as an undergrad in Spring 2007. Made some modifications to undertaker for analyzing packing of aromatic rings in BME 220 project, currently working on per-residue model quality assessment using undertaker.

Steven Hobbs

Started as an undergrad Winter 2008, working on trying to get Rprop implemented in predict-2nd.

Alex Atkins

Started as an undergrad in Winter 2008 in BME 220, working on trying to get HMM-HMM scoring and alignment working in SAM's hmmscore.

Dietlind's students

Thomas Juettemann

Dietlind's student from Edinburgh, visiting UCSC starting July 2007.

Research Topics

We have participated in all but the first of the CASP (Critical Assessment of Structure Prediction) experiments and have done well in CASP2, CASP3, CASP4, CASP5, CASP6, and CASP7. All our working notes and files for CASP6 and CASP7 are available on the web at http://www.soe.ucsc.edu/~karplus/casp6 and http://www.soe.ucsc.edu/~karplus/casp7 A rough assessment of the CASP6 results is available in http://www.soe.ucsc.edu/~karplus/casp6/assessment.html

Publications

Software and services available

Released Software:

SAM

The premier suite of hidden Markov Model tools, originally created by Anders Krogh, extended and maintained by Richard Hughey.

gen_sequence

Open-source (C) code for generating random sequences, also includes generating random numbers from beta and Gaussian distributions, and random vectors from mixtures of Dirichlet distributions.

Unreleased Software: (pointers needed for UCSC access only)

"ultimate" C++ class library

undertaker

predict-2nd

estimate-dist

correlated-columns

Web Services and databases

SAM-T06 alignment, HMM, database query, secondary structure predictions, residue-residue contact prediction, 3D-structure prediction

UCSC's SAM-T06 method for iterative SAM HMM construction and remote homology detection and protein structure prediction updates SAM-T02 by using more sensitive iterated search, more local structure prediction, residue-residue contact prediction, and full 3D structure prediction. information in its scoring functions. SAM-T99, SAM-T02, and SAM-T06 were all server entries to CASP7, and SAM-T06 was the best of the three.

Submit a target protein sequence in FASTA format and receive a web page full of predictions. This is our current best-performing server.

SAM-T02 alignment, HMM, database query, secondary structure predictions and more

UCSC's SAM-T02 method for iterative SAM HMM construction and remote homology detection and protein structure prediction updates SAM-T99 by using predicted secondary structure information in its scoring functions. Both SAM-T99 and SAM-T02 are "automatic" entries to CASP5 and CASP6.

Submit a target protein sequence in FASTA format and receive SAM-T02 alignment, HMM, protein database query, secondary structure predictions, sequence logos and pairwise alignments of target to top database hits.

Yeast protein predictions

We have pre-computed SAM-T02 predictions for all the ORFs of S. cerervisiae, and created a web page similar to the results returned by the SAM-T02 server. The web pages are not currently indexed---to find a protein like YBL008W you have to go to the subdirectory YBL0/YBL008W and get the summary.html file. We update some of the yeast predictions each quarter, based on new structures released in PDB. Some of the newer updates use the SAM-T06 protocol.

SAM-T99 alignment, HMM, protein database query, and secondary structure prediction

Submit a protein sequence (or alignment) in FASTA format and receive SAM-T99 alignment, HMM, database hits, and secondary structure prediction. This site has been mostly superseded by the SAM-T02 site, but we'll keep it running as long as we can, since several meta-servers use it. We urge anyone doing new work to use the SAM-T06 server instead, since it produces more accurate results. The T99 server may go away as we move to a new cluster, as the code is very messy and hard to port.

Lab Alumnæ and Alumni

Martin Madera

Postdoc from May 2006 to Apr 2008. Participated in CASP7. Mainly spent his time writing grant proposals in an unsuccessful attempt to get some stable funding for himself. Revamped our fold-recognition and alignment tests.

Martin Paluszewski

Pawel Winter's student from Denmark, visited UCSC for 6 months, starting July 2007. Working on extracting constraints from alignments.

Joanna Sharman

Dietlind's student from Edinburgh, visited UCSC for a short time starting August 2007.

Pinal Kanabar

MS student. Started work on testing a new H-bond-based local-structure alphabet in Spring 2005 as prospective student (now Grant's project). Participated parttime in CASP7.

Greg Dougherty

MS student. Working on interfacing ProteinShop and undertaker (mainly as BME 220 project, W06).

Zack Sanborn

PhD student. Lab rotation Winter 06, worked on protein design using back-propagation in neural nets and RosettaDesign. Participated parttime in CASP7.

Chris Wong

MS student. Worked on sequence recovery testing of Design1st in Predict-2nd. Participated parttime in CASP7.

Mark Mitchell

PhD student. Lab rotation Winter 06, worked on confirming that gamma distribution was appropriate for mutual information null model. (deceased)

Oscar Hur, PhD (postdoc, roughly 2002-2005)

Published paper on converting hydrogen distance restraints into heavy-atom constraints. Working on an HMM for detecting and aligning TIM barrels.

Sol Katzman

bioinformatics grad student---worked for group for CASP6 (Jan-Sept 2005), but has chosen a different lab after first-year rotations.

Wing Wong (2004-2005)

MS student in CS at San Jose State. Worked on profile-profile alignment in SAM, but decided to stick with CS.

Jes Frellsen

undergraduate from Denmark (Winter+Spring 2005). Worked on using backpropagation in local-structure neural nets to do protein design.

NavyaSwetha Davuluri

Undergrad. Working on tuning undertaker cost function for rotamer optimization. Participated in CASP7.

Erich Blume

Undergrad. Working on tuning undertaker cost function for rotamer optimization.

Sylvia Do

Undergrad. Participated in CASP7.

Crissan Harris.

Undergrad. SURF-IT student. Participated in CASP7.

Cynthia Hsu.

Undergrad. SURF-IT student. Participated in CASP7.

Suma Potluri

MS student in computer science. Started project in W06 on converting neural-net probability vector output for burial alphabet to continuous prediction for burial

Ron Chao

bioinformatics grad student. Winter 2005. Was going to look at template or alignment selection for close homologs, but drifted off to other labs.

Cameron Reid

has BS in biology and CS from UCSC. Took BME 100. Spring 2005. Started working on using inverse kinematics to do "wiggling without breaking" as a conformation-change operator in undertaker, but drifted off before implementing anything.

Carl Gorringe

Undergraduate (inherited from Carol Rohl's lab). Winter 2005. Started working on a project with David Bernick to predict functional residues from differences in conservation between homologs and "morphologs", but dropped the project due to overload.

Rachel Karchin

A UCSC undergrad and grad student. worked on CASP4 and CASP5. Finished her PhD under Karplus's supervision in June 2003. Currently working as a postdoc in Šali's lab at UCSF.

Christian Barrett

Finished his PhD under Karplus's supervision in 2001. Worked for a year in Iceland and is currently doing a postdoc in Palsson's lab at UCSD. Participated in CASP-2 and CASP-3.

Melissa Cline

jointly advised with David Haussler and Lydia Gregoret, worked with Karplus on several projects. Finished her PhD in June 2000. Participated in CASP-2 and CASP-3.

Kimmen Sjölander

jointly advised with David Haussler, but worked with Karplus on several projects. Finished her PhD in 1997. Currently on the faculty at UC Berkeley. Participated in CASP-2.

Leslie Grate

advised by Richard Hughey, did at least one project with Karplus (finding homolog of mamalian antizyme in S. pombe, but not S. cerevisiae). Finished his PhD in 1999. Currently at Lawrence Berkeley Lab, but looking for a more productive research position. Provided some software for CASP-2 and CASP-3.

Mark Diekhans

advised by David Haussler, but has provided some software support for the Karplus lab, mainly in the form of scripts for downloading and parsing PDB files. Has also worked on secondary-structure prediction using posterior decoding of HMMs.

Sugato Basu

Finished his Master's degree in 2000. Worked on the Transform class in the C++ library and some other fundamental code for the undertaker program. Now in Raymond Mooney's machine-learning group at UT Austin, working on semi-supervised clustering, both of text and microarray data, PhD expected summer 2005.

Birong Hu

Finished her master's degree in 2000. Worked on using BaliBase to test SAM-T99 as a multiple-alignment method. Had a prior PhD in biology from UCLA.

David Lin

jointly advised by Haussler. Finished his Masters in 1999, worked with Karplus on converting protein HMMs to models for searching EST databases.

Pernille Nielsen

a visiting grad student (Oct 04-Feb 05), from Anders Krogh's lab in Denmark. Working on support-vector machines and HMMs to classify short ORFs as protein-coding or non-protein coding.

Marcia Soriano

bioinformatics senior, evaluating secondary-structure predictors. Graduated March 05.

Bret Barnes, undergrad

bioinformatics senior, track weighting for multi-track HMMs to optimize alignment. Graduated 2005.

Adetunde Famakinwa Adekunle (Tunde).

Undergrad summer 2005. Worked on training local-structure nerual nets.

Rudy Ortegon.

Undergrad summer 2005. Worked on implementing priority queues.

Mamie Jallow

Undergrad from Univ of Washington. summer 2005. Worked on structure predictions for extracellular domains of chemotaxis proteins from Vibrio cholerae.

Don Speck

Don was never officially part of the Karplus group, but did a lot of work across the hall in the Kestrel lab and frequently interacted with Richard Hughey and Kevin Karplus. One of his projects (on reduced-space sequence alignment) was particularly important to the SAM suite. He is now working as a VLSI designer.

Spencer Tu

Worked on a general HMM program for several years. Architect of the SAM-T99 web service. Participated in CASP-4.

Jenny Draper

bioinformatics grad student, currently working in Karen Ottemann's lab. Participated in CASP-5 and CASP-6.

Jonathan Casper

computer engineering grad student. Participated in CASP-5. Did some work on scoring hydrogen bonds.

Martina Koeva

bioinformatics grad student, currently working in Josh Stuart's lab. Participated in CASP-6 predictions.

Yael Mandel-Gutfreund

Was a postdoc for Lydia Gregoret, but supervised by Karplus for a year after Gregoret left UCSC. Created the str and str2 local structure alphabets. Participated in CASP-5. Now on the faculty at the Technion Institute of Technology.

SoE home

Kevin Karplus's home page

BS, MS, and PhD programs

Karplus's lab page

UCSC Bioinformatics research

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