Abstract

This application has three major aims that exploit the use of mathematical programming tools for biophysically motivated problems. The first goal is the refinement of protein structures that are obtained from homology. Structures based on homology are rarely of atomic resolution; a resolution which is necessary for detailed modeling of protein function, and for the design of drug molecules. Based on mathematical programming approach a new class of energy functions, suitable for the refinement problem, will be designed. The second goal is to investigate a new type of network; the network of sequence flow between protein structures. We examine the process in which new sequences, generated by point mutations, remain in the current fold, or switch to other stable structures (we exclude sequences with no stable fold). The adjustments to the structure are accepted or rejected based on stability criterion. The net. work defines a master equation which makes it possible to investigate past (ancient) folds, and future structures that serve as attractors.
The third aim examines the network of protein-protein (physical) interactions and will be examined with bioinformatics and biophysical approaches. Comparison will be made between the network of sequence flow and the network of protein-protein interactions to better understand the evolution of biological mechanisms and recognition.

Public Health Relevance

The design of new algorithms to predict protein structures and protein-protein interactions is likely to help with the design of new drug molecules. ? ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM067823-06
Application #
7466765
Study Section
Macromolecular Structure and Function E Study Section (MSFE)
Program Officer
Wehrle, Janna P
Project Start
2004-02-01
Project End
2011-05-31
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
6
Fiscal Year
2008
Total Cost
$305,195
Indirect Cost

  Institution

Name
University of Texas Austin
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712

  Publications

Viswanath, Shruthi; Dominguez, Laura; Foster, Leigh S et al. (2015) Extension of a protein docking algorithm to membranes and applications to amyloid precursor protein dimerization. Proteins 83:2170-85
Elber, Ron (2015) From an SNP to a Disease: A Comprehensive Statistical Analysis. Structure 23:1155
Burke, Sean; Elber, Ron (2012) Super folds, networks, and barriers. Proteins 80:463-70
Ravikant, D V S; Elber, Ron (2011) Energy design for protein-protein interactions. J Chem Phys 135:065102
Adamczak, Rafal; Pillardy, Jaroslaw; Vallat, Brinda K et al. (2011) Fast geometric consensus approach for protein model quality assessment. J Comput Biol 18:1807-18
Phatak, Mukta; Adamczak, Rafa?; Cao, Baoqiang et al. (2011) Solvent and lipid accessibility prediction as a basis for model quality assessment in soluble and membrane proteins. Curr Protein Pept Sci 12:563-73
Cao, Baoqiang; Elber, Ron (2010) Computational exploration of the network of sequence flow between protein structures. Proteins 78:985-1003
Lam, Ying Wai; Yuan, Yong; Isaac, Jared et al. (2010) Comprehensive identification and modified-site mapping of S-nitrosylated targets in prostate epithelial cells. PLoS One 5:e9075
Porollo, Aleksey; Meller, Jaroslaw (2010) POLYVIEW-MM: web-based platform for animation and analysis of molecular simulations. Nucleic Acids Res 38:W662-6
Swaminathan, Karthikeyan; Adamczak, Rafal; Porollo, Aleksey et al. (2010) Enhanced prediction of conformational flexibility and phosphorylation in proteins. Adv Exp Med Biol 680:307-19

Showing the most recent 10 out of 24 publications