Accurate Fitting SAXS Curves with NMR Structure Ensembles

KŘENEK, Aleš, Karel KUBÍČEK, Richard ŠTEFL and Jiří FILIPOVIČ. Accurate Fitting SAXS Curves with NMR Structure Ensembles. Online. In Simon Lin, Vicky Huang. Proceedings of International Symposium on Grids and Clouds 2015. Pissa: Proceedings of Science, 2015, p. nestránkováno, 9 pp. ISSN 1824-8039.

Basic information

• Original name: Accurate Fitting SAXS Curves with NMR Structure Ensembles
• Authors: KŘENEK, Aleš (203 Czech Republic, guarantor, belonging to the institution), Karel KUBÍČEK (203 Czech Republic, belonging to the institution), Richard ŠTEFL (203 Czech Republic, belonging to the institution) and Jiří FILIPOVIČ (203 Czech Republic, belonging to the institution).
• Edition: Pissa, Proceedings of International Symposium on Grids and Clouds 2015, p. nestránkováno, 9 pp. 2015.
• Publisher: Proceedings of Science

Other information

• Original language: English
• Type of outcome: Proceedings paper
• Field of Study: 10600 1.6 Biological sciences
• Confidentiality degree: is not subject to a state or trade secret
• Publication form: electronic version available online
• WWW: URL
• RIV identification code: RIV/00216224:14610/15:00083645
• Organization unit: Institute of Computer Science
• ISSN: 1824-8039
• Keywords (in Czech): saxs; nmr; ensamble fit
• Keywords in English: saxs; nmr; ensamble fit
• Tags: rivok
• Tags: International impact, Reviewed

Abstract

Typical NMR analyses of a biomolecule yields a set of up to few dozens candidate 3D structures of the analyzed molecule without any clues to discriminate among them further. A parallel SAXS experiment on the same sample can be used for this purpose. Previous implementations of “ensemble fit” (search for a mix of molecular conformations which matches the SAXS curve) were designed to choose from a huge ensemble generated by molecular dynamics. Therefore the methods must trade off accuracy for manageable speed, and they end up in mixing curves computed with rather different values of parameters which have physical meaning, which should be avoided. On the contrary, with a relatively small input set of candidate NMR structures we take a more accurate approach. Both the model parameters, considered globally now, and weights of individ- ual candidate structures (reflecting their presence in the solution) become independent variables of a multidimensional global optimization problem; the optimized value is the accuracy of the fit to the experimental data. The optimization must escape from traps of many local minima there- fore we use Monte Carlo with stochastic tunnelling. The method also offers opportunities for parallelization. The final issue is user friendliness of the entire workflow, which is quite complex, involving several programs to be run, handling different file formats, and setting multiple parameters, ending up with visualization of results. We outline design of a web portal hiding these complexities to the end user.

Links

• MUNI/M/1038/2013, interní kód MU: Name: Development of new interdisciplinary approaches to study function and regulation of transcriptome

Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects