Computational studies of protein helix kinks

• Main Author: Wilman, Henry R
• Format: Dissertation
• Language: English
• Published: University of Oxford 2014
• Subjects: Bioinformatics (biochemistry); Bioinformatics (life sciences); Bioinformatics (technology); Computational chemistry; crowdsourcing; Helix; Kink; Life Sciences; Mathematical genetics and bioinformatics (statistics); Membrane proteins; Physical Sciences; Polymers Amino acid and peptide chemistry; Protein; Protein chemistry; protein structure prediction; Secondary structure; Structural biology; Technology and Applied Sciences

Kinks are functionally important structural features found in the alpha-helices of many proteins, particularly membrane proteins. Structurally, they are points at which a helix abruptly changes direction. Previous kink definition and identification methods often disagree with one another. Here I describe three novel methods to characterise kinks, which improve on existing approaches. First, Kink Finder, a computational method that consistently locates kinks and estimates the error in the kink angle. Second the B statistic, a statistically robust method for identifying kinks. Third, Alpha Helices Assessed by Humans, a crowdsourcing approach that provided a gold-standard data set on which to train and compare existing kink identification methods. In this thesis, I show that kinks are a feature of long -helices in both soluble and membrane proteins, rather than just transmembrane -helices. Characteristics of kinks in the two types of proteins are similar, with Proline being the dominant feature in both types of protein. In soluble proteins, kinked helices also have a clear structural preference in that they typically point into the solvent. I also explored the conservation of kinks in homologous proteins. I found examples of conserved and non-conserved kinks in both the helix pairs and the helix families. Helix pairs with non-conserved kinks generally have less similar sequences than helix pairs with conserved kinks. I identified helix families that show highly conserved kinks, and families that contain non-conserved kinks, suggesting that some kinks may be flexible points in protein structures.