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
Register for class
Graduate students attending the protein structure club and lab group meetings should register for BME 281K (Seminar on Protein Structure Prediction). This is in addition to any independent study or thesis work they are doing with me.Current projects
There are always more projects to do than people to do them. I used to keep a partial list of projects that need doing at http://www.soe.ucsc.edu/~karplus/protein-projects.html but I have not been keeping it up to date. Instead, I've been creating lists for the BME 220 (Protein Informatics) class:- 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, predicting function using structure
- 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.
- 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.
- 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
The lab mainly works on protein-structure prediction, though we hope to get into protein design in the near future. We work on almost all aspects of protein-structure prediction including remote homology detection using interated search and hidden Markov models, alignment of sequences to structures using multi-track hidden Markov models, prediction of local structure properties using neural nets, prediction of residue contacts using mutual information, and tertiary structure prediction using conformation generation and scoring.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, CASP7, and CASP8. All our working notes and files for CASP6, CASP7, and CASP8 are available on the web at http://www.soe.ucsc.edu/~karplus/casp6 http://www.soe.ucsc.edu/~karplus/casp7 http://www.soe.ucsc.edu/~karplus/casp8
Publications
Publications are mainly on Kevin Karplus's paper list.Software and services available
Released Software:
We currently have two software packages available:- 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)
We hoped to be able to distribute the following software in the near future, but NIH turned down a grant application to fix them up enough to make them open-source, so it is not clear when we'll have the spare resources to do it. In the meantime, we are allowing access to the uncleaned-up code, for those with the fortitude to modify, install, and compile it themselves without assistance from us:- "ultimate" C++ class library http://compbio.soe.ucsc.edu/~karplus/ultimate
- undertaker http://compbio.soe.ucsc.edu/~karplus/undertaker
- predict-2nd http://compbio.soe.ucsc.edu/~karplus/predict-2nd
- estimate-dist http://compbio.soe.ucsc.edu/~karplus/estimate-dist
- correlated-columns (sorry, even my copy isn't up to date---I hope to have time to copy it from the grad student and check it in Spring 2009).
- undertaker http://compbio.soe.ucsc.edu/~karplus/undertaker
Web Services and databases
- SAM-T08 alignment, HMM, database query, secondary structure predictions, residue-residue contact prediction, 3D-structure prediction
-
UCSC's SAM-T08 method for iterative SAM HMM
construction and remote homology detection and protein structure
prediction updates SAM-T06 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-T02, SAM-T06, SAM-T08 were all server entries to CASP8, and
SAM-T08 was by far 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-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, but has been superceded by SAM-T08.
This site is obsolete and is maintained only for historical comparison.
- 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.
This site is obsolete and is maintained only for historical comparison.
- 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 year, 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
- This site has been turned off, as it was too difficult to maintain every time we changed any software on the cluster. It accepted a protein sequence (or alignment) in FASTA format and returned SAM-T99 alignment, HMM, database hits, and secondary structure prediction.
Lab Alumnæ and Alumni
This list is not really complete. I have only recently started keeping the list, and my memory is notoriously poor. I know I have omitted many undergrads who worked with me, and I relied on publication lists to try to get the complete list of grad students who worked with me, so anyone who didn't publish probably got overlooked. I've also limited the list to bioinformatics projects, omitting students who worked with me back when I did VLSI design and CAD for VLSI.- Josue Samayoa
PhD student (inherited from Carol
Rohl's lab). Worked with Carol on using residual dipolar coupling
data to aid in choosing alignments of targets to templates.
Worked with Fitnat Yldiz on simple repeats and short proteins in
Vibrio cholerae.
Finished PhD, July 2009.
Thesis title:" A comparative genomic analysis of simple repeat
motifs and short proteins in prokaryotes."
Gone to work as postdoc in Rachel Karchin's lab.
- Chirag X. Sharma
Started as an undergrad June 2008, learning to do protein structure
prediction for CASP8. Started working on Pyrobaculum aerophilum
proteins (Pryobaculum-specific proteins) August 2008.
- 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.
- Javier Castellanos
Visiting grad student from University of Chile, mid-Jan to mid-March 2009.
Javier worked on the Qcost cost functions for undertaker (comparing
models based on differences in distances).
He also started work in undertaker to convert CA-only models to
full-atom models.
- Allison Weis
SURF-IT student 23 June 2008–22 August 2008.
Worked on GPCR charge distribution for Glen Milhauser and malarial
proteins for Dietlind Gerloff.
- Firas Khatib
-
PhD student (inherited from Carol Rohl's lab).
Participated in CASP6 with Carol, CASP7 with me. Did a tiny bit
in CASP8.
Finished thesis on finding knots and slip-knots in protein conformations
generated by structure prediction methods on 30 July 2008.
Thesis title: "Topological Filters for use with Protein Structure Prediction".
Gone for a postdoc in David Baker's lab.
- 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.
Went to a postdoc with Julian Gough, who had
more stable funding.
- Martin Paluszewski
Pawel Winter's student from Denmark, visited UCSC for 6 months,
starting July 2007. Worked on extracting constraints from
alignments, and his methods were tested in CASP8 as the
SAM-T08-MQAO model-quality assessment. They were also part of the
SAM-T08-MQAU and SAM-T08-MQAC methods. Started a postdoc in
Anders Krogh's lab.
- 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.
- Chris Dragon
- Computer science undergrad, Fall 2003. Rewrote a2m2html, adding links to NIH for sequences and taxonomy.
- Rachel Karchin
- A UCSC undergrad and grad student. worked on CASP4 and CASP5. Finished her PhD under Karplus's supervision in June 2003. Thesis title: "Local Statistical Dependencies in Protein Structure: Discovery, Evaluation, Prediction and Applications". Did a couple of years as a postdoc in Šali's lab at UCSF, then got a faculty position at Johns Hopkins.
- Christian Barrett
- Finished his PhD under Karplus's supervision in Sept. 2001. "Investigation of non-pairwise protein structure score functions using Thesis title: sets of decoy structures". 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. Thesis title: "Protein Sequence Alignment Reliability: Prediction and Measurement".
- 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. Thesis title: "Computer Analysis of RNA". Did a postdoc at Lawrence Berkeley Lab, then one in Manny's lab at UCSC. 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.
- Martina Koeva
- bioinformatics grad student, currently working in Josh Stuart's lab. Participated in CASP-6 predictions.
- 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.
- Spencer Tu
- Worked on a general HMM program for several years.
Architect of the SAM-T99 web service.
Participated in CASP-4.
- Scot Kennedy
- Undergraduate, 2002?. Wrote initial version of a2m2html.
- 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.
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| Karplus's lab page | UCSC Bioinformatics research |
Questions about page content should be directed to
Kevin Karplus
Biomolecular Engineering
University of California, Santa Cruz
Santa Cruz, CA 95064
USA
karplus@soe.ucsc.edu
1-831-459-4250
318 Physical Sciences Building
