Upcoming Colloquia

All seminars will be held in the MBI Lecture Hall - Jennings Hall, Room 355 - unless otherwise noted.

April 06, 2015 3:00 - 3:50PM
Host: Greg Rempala

The three-dimensional (3D) configuration of chromosomes within the eukaryote nucleus is consequential for several cellular functions, including gene expression regulation, and is also associated with cancer-causing translocation events.   While visualization of such architecture remains limited to low resolutions, the ability to infer structures at high resolution has been enabled by recently-devised chromosome conformation capture assays.  In particular, when coupled with next generation sequencing, such methods yield a genome-wide inventory of chromatin interactions.   Various algorithms have been advanced to operate on such data to produce reconstructed 3D configurations.  Several studies have shown that such reconstructions provide added value over raw interaction data with respect to downstream biological analysis.  

However, such added value has yet to be fully realized for higher eukaryotes since no high resolution genome-wide reconstructions have been inferred for these organisms because of computational bottlenecks and organismal complexity.  After overviewing existing reconstruction approaches we propose a two-stage algorithm, deploying multi-dimensional scaling and Procrustes transformation, that overcomes these barriers. 3D architectures for mouse and human are presented and methods for evaluating these solutions discussed.  Finally, reverting to yeast, we demonstrate the advantages bestowed by 3D structures with respect to identifying co-regulatory elements.

April 20, 2015 3:00 - 3:50PM
Host: Andrej Rotter

 

We have developed and combined several novel methods to improve protein structure prediction from the amino acid sequence, and modeling of protein dynamics. One of the most promising developments in protein structure prediction are many-body potentials that take into account dense packing, and cooperativity of interactions in protein cores. We developed a method that uses whole protein information filtered through machine learners to score protein models based on their likeness to native structures. These results were published by us [1], and tested successfully in CASP 9, where our prediction group 4_BODY_POTENTIALS was among top three predictors in the category of template-free modeling for the most difficult targets. Recently we have significantly improved our potentials by considering electrostatic interactions and residue depth and used them for the prediction of protein structure and blind tested them in CASP 10. Our prediction group Kloczkowski_Lab was ranked as the third one in prediction of structure (based on the single model) for all targets, and ranked also as the second one for template free-modeling (see: http://www.predictioncenter.org/casp10/groups_analysis.cgi ) [2]. By combing statistical contact potentials with entropies from the elastic network models of proteins we can compute free energy and improve coarse-grained modeling of protein structure and dynamics [3]. The consideration of protein flexibility and its fluctuational dynamics improves protein structure prediction, leads to a better refinement of computational models of proteins, and significantly improves protein docking [4,5]. We studied also the self-assembly of FVFLM peptide and its influence on the kinetics of Aβ16-20 oligomerization.

1. P. Gniewek, A. Kolinski, R.L. Jernigan, and A. Kloczkowski, Proteins 79, 1923 (2011)

2. E. Faraggi and A. Kloczkowski, Proteins  82, 3170-6, (2014)

3. M.T. Zimmermann, S.P. Leelananda, A. Kloczkowski, and R.L. Jernigan, JPC B116, 6725 (2012)

4. P. Gniewek, A. Kolinski, R.L. Jernigan, and A. Kloczkowski, JCP 136, 195101 (2012)

5. P. Gniewek, A. Kolinski, R.L. Jernigan, and A. Kloczkowski, Proteins 80, 335 (2012)

TBD
August 31, 2015 3:00 - 3:50PM
Host: TBD

Abstract not submitted.

TBD
September 21, 2015 3:00 - 3:50PM
Host: TBD

Abstract not submitted.

TBD
October 05, 2015 3:00 - 3:50PM
Host: TBD

Abstract not submitted.

TBD
October 19, 2015 3:00 - 3:50PM
Host: TBD

Abstract not submitted.

TBD
November 02, 2015 3:00 - 3:50PM
Host: TBD

Abstract not submitted.

TBD
November 09, 2015 3:00 - 3:50PM
Host: TBD

Abstract not submitted.

TBD
March 28, 2016 3:00 - 3:50PM
Host: TBD

Abstract not submitted.