Computational geometry for the determination of biomolecular structures
- Authors
- Publication Date
- Apr 27, 2017
- Source
- Kaleidoscope Open Archive
- Keywords
- Language
- English
- License
- Unknown
- External links
Abstract
Structural biology has allowed us expand our knowledge of living organisms. It is defined as the investigation of the structure and function of biological systems at the molecular level. Studying a biomolecule's structure offers insight into its geometry, as angles and distances between the biomolecule's atoms are measured in order to determine the biomolecular structure. The values of these geometrical parameters may be obtained from biophysical techniques, such as X-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy. One of the most used methods to calculate protein structures from geometric restraints is simulated annealing. This method does not guarantee an exhaustive sampling of protein conformational space, which is a shortcoming as one protein may adopt multiple functional conformations, and it is important to determine them exhaustively. In this PhD project, the efficiency of a new method - derived from operations research and computational geometry - is studied in order to answer this question: How does this method explore the conformational spaces of small proteins? This method - implemented within the iBPprot software framework - treats protein structure determination as a distance geometry problem, which the interval branch-and-prune algorithm tries to solve by the full exploration of its solutions space. The results obtained by iBPprot on a set of test proteins, with sizes ranging from 24 to 120 residues and with known structures, are analyzed here. Using short-range exact distance restraints, it was possible to rebuild the structure of all protein targets, and for many of them it was possible to exhaustively explore their conformational spaces. In practice, it is not always possible to obtain exact distance restraints from experiments. Therefore, this method was then tested with interval data restraints. In these cases, iBPprot permitted the sampling of the positions of more than 70% of the atoms constituting the protein backbone for most of the targets. Furthermore, conformations whose r.m.s. deviations closer than 6 Angstrom to the target ones were obtained during the conformational space exploration. The quality of the generated structures was satisfactory with respect to Ramachandran plots, but needs improvement because of the presence of steric clashes in some conformers. The runtime for most performed calculations was competitive with existing structure determination method...
