β-Barrel transmembrane proteins: Geometric modelling, detection of transmembrane region, and structural properties

摘要

The location of the membrane lipid bilayer relative to a transmembrane protein structure is important in protein engineering. Since it is not present on the determined structures, it is essential to automatically define the membrane embedded protein region in order to test mutation effects or to design potential drugs. β-Barrel transmembrane proteins, present in nature as outer membrane proteins (OMPs), comprise one of the two transmembrane protein fold classes. Lately, the number of their determined structures has increased and this enables the implementation and evaluation of structure-based annotation methods and their more comprehensive study. In this paper, we propose two new algorithms for (ⅰ) the geometric modelling of β-barrels and (ⅱ) the detection of the transmembrane region of a β-barrel transmembrane protein. The geometric modelling algorithm combines a non-linear least square minimization method and a genetic algorithm in order to find the characteristics (axis, radius) of a shape with axial symmetry which best models a β-barrel. The transmembrane region is detected by profiling the external residues of the β-barrel along its axis in terms of hydrophobicity and existence of aromatic and charged residues. TbB-Tool implements these algorithms and is available in http://www.di.uoa.gr/～ivalavan/TbB_Tool.htm. A non-redundant set of 22 OMPs is used in order to evaluate the algorithms implemented and the results are very satisfying. In addition, we quantify the abundance of all amino acids and the average hydrophobicity for external and internal β-stranded residues along the axis of β-barrel, thus confirming and extending other researchers' results.