Dartmouth logo Dartmouth College Computer Science
Technical Report series
CS home
TR home
TR search TR listserv
By author: A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
By number: 2017, 2016, 2015, 2014, 2013, 2012, 2011, 2010, 2009, 2008, 2007, 2006, 2005, 2004, 2003, 2002, 2001, 2000, 1999, 1998, 1997, 1996, 1995, 1994, 1993, 1992, 1991, 1990, 1989, 1988, 1987, 1986

Graph algorithms for NMR resonance assignment and cross-link experiment planning
Fei Xiong
Dartmouth TR2010-675

Abstract: The study of three-dimensional protein structures produces insights into protein function at the molecular level. Graphs provide a natural representation of protein structures and associated experimental data, and enable the development of graph algorithms to analyze the structures and data. This thesis develops such graph representations and algorithms for two novel applications: structure-based NMR resonance assignment and disulfide cross-link experiment planning for protein fold determination. The first application seeks to identify correspondences between spectral peaks in NMR data and backbone atoms in a structure (from x-ray crystallography or homology modeling), by computing correspondences between a contact graph representing the structure and an analogous but very noisy and ambiguous graph representing the data. The assignment then supports further NMR studies of protein dynamics and protein-ligand interactions. A hierarchical grow-and-match algorithm was developed for smaller assignment problems, ensuring completeness of assignment, while a random graph approach was developed for larger problems, provably determining unique matches in polynomial time with high probability. Test results show that our algorithms are robust to typical levels of structural variation, noise, and missings, and achieve very good overall assignment accuracy. The second application aims to rapidly determine the overall organization of secondary structure elements of a target protein by probing it with a set of planned disulfide cross-links. A set of informative pairs of secondary structure elements is selected from graphs representing topologies of predicted structure models. For each pair in this ``fingerprint'', a set of informative disulfide probes is selected from graphs representing residue proximity in the models. Information-theoretic planning algorithms were developed to maximize information gain while minimizing experimental complexity, and Bayes error plan assessment frameworks were developed to characterize the probability of making correct decisions given experimental data. Evaluation of the approach on a number of structure prediction case studies shows that the optimized plans have low risk of error while testing only a very small portion of the quadratic number of possible cross-link candidates.

Note: Ph.D Dissertation. Advisor: Chris Bailey-Kellogg.

PDF PDF (2304KB)

Bibliographic citation for this report: [plain text] [BIB] [BibTeX] [Refer]

Or copy and paste:
   Fei Xiong, "Graph algorithms for NMR resonance assignment and cross-link experiment planning." Dartmouth Computer Science Technical Report TR2010-675, June 2010.

Notify me about new tech reports.

Search the technical reports.

To receive paper copy of a report, by mail, send your address and the TR number to reports AT cs.dartmouth.edu

Copyright notice: The documents contained in this server are included by the contributing authors as a means to ensure timely dissemination of scholarly and technical work on a non-commercial basis. Copyright and all rights therein are maintained by the authors or by other copyright holders, notwithstanding that they have offered their works here electronically. It is understood that all persons copying this information will adhere to the terms and constraints invoked by each author's copyright. These works may not be reposted without the explicit permission of the copyright holder.

Technical reports collection maintained by David Kotz.