Journal of Chemical Information and Modeling, 2010
Although the α-helical secondary structure of proteins is well-defined, the exact causes and stru... more Although the α-helical secondary structure of proteins is well-defined, the exact causes and structures of helical kinks are not. This is especially important for transmembrane (TM) helices of integral membrane proteins, many of which contain kinks providing functional diversity despite predominantly helical structure. We have developed a Monte Carlo method based algorithm, MC-HELAN, to determine helical axes alongside positions and angles of helical kinks. Analysis of all nonredundant high-resolution α-helical membrane protein structures (842 TM helices from 205 polypeptide chains) revealed kinks in 64% of TM helices, demonstrating that a significantly greater proportion of TM helices are kinked than those indicated by previous analyses. The residue proline is over-represented by a factor >5 if it is two or three residues C-terminal to a bend. Prolines also cause kinks with larger kink angles than other residues. However, only 33% of TM kinks are in proximity to a proline. Machine learning techniques were used to test for sequence-based predictors of kinks. Although kinks are somewhat predicted by sequence, kink formation appears to be driven predominantly by other factors. This study provides an improved view of the prevalence and architecture of kinks in helical membrane proteins and highlights the fundamental inaccuracy of the typical topological depiction of helical membrane proteins as series of ideal helices.
ISCA International Conference on Parallel and Distributed Computing Systems, 2005
Inferring phylogenetic relationships between sequences is a difficult and interesting problem. As... more Inferring phylogenetic relationships between sequences is a difficult and interesting problem. Assuming that there is enough phylogenetic signal in biological sequence to resolve every tree bifurcation, the resulting tree is a representation of the vertical descent history of a gene. A popular method to evaluate a candidate phylogenetic tree uses the likelihood of the data, given an empirical model of
Journal of Chemical Information and Modeling, 2010
Although the α-helical secondary structure of proteins is well-defined, the exact causes and stru... more Although the α-helical secondary structure of proteins is well-defined, the exact causes and structures of helical kinks are not. This is especially important for transmembrane (TM) helices of integral membrane proteins, many of which contain kinks providing functional diversity despite predominantly helical structure. We have developed a Monte Carlo method based algorithm, MC-HELAN, to determine helical axes alongside positions and angles of helical kinks. Analysis of all nonredundant high-resolution α-helical membrane protein structures (842 TM helices from 205 polypeptide chains) revealed kinks in 64% of TM helices, demonstrating that a significantly greater proportion of TM helices are kinked than those indicated by previous analyses. The residue proline is over-represented by a factor >5 if it is two or three residues C-terminal to a bend. Prolines also cause kinks with larger kink angles than other residues. However, only 33% of TM kinks are in proximity to a proline. Machine learning techniques were used to test for sequence-based predictors of kinks. Although kinks are somewhat predicted by sequence, kink formation appears to be driven predominantly by other factors. This study provides an improved view of the prevalence and architecture of kinks in helical membrane proteins and highlights the fundamental inaccuracy of the typical topological depiction of helical membrane proteins as series of ideal helices.
ISCA International Conference on Parallel and Distributed Computing Systems, 2005
Inferring phylogenetic relationships between sequences is a difficult and interesting problem. As... more Inferring phylogenetic relationships between sequences is a difficult and interesting problem. Assuming that there is enough phylogenetic signal in biological sequence to resolve every tree bifurcation, the resulting tree is a representation of the vertical descent history of a gene. A popular method to evaluate a candidate phylogenetic tree uses the likelihood of the data, given an empirical model of
Uploads
Papers by Christian Blouin