From Protein Structure to Function with Bioinformatics.pdf

4 Membrane Protein Structure Prediction 107growth factor-receptor tyrosine kinase protein (Ghosh et al. 2001), Bruton’s tyrosinekinase (Mahajan et al. 1999) and Janus kinase 3 (Sudbeck et al. 1999).Ab initio modelling, or de novo modelling, involves the construction of a 3Dmodel in the absence of any structural data relating to the target protein or ahomologue. Research has focused in three main areas: alternate lower-resolutionrepresentations of proteins, accurate energy functions, and efficient sampling methods.While most methods address globular proteins, some efforts have been directedat TM protein structure prediction.ROSETTA (Rohl et al. 2004) is an ab initio modelling server that uses potentialfunctions for computing the lowest energy structure for an amino acid sequence.Feedback from the prediction is used continually to improve potential functions andsearch algorithms. A modified version of the ROSETTA algorithm (Barth et al.2007) uses an energy function that describes membrane intraprotein interactions atatomic level and membrane protein/lipid interactions implicitly, while treatinghydrogen bonds explicitly. Results suggest that the model captures the essentialphysical properties that govern the solvation and stability of membrane proteins,allowing the structures of small TM protein domain (