Simulation of the packing of transmembrane alpha-helices.

The aim of this study is to generate initial candidate models for bundles of transmembrane helices. Such models may then be further refined by eg. molecular dynamics simulations. Each helix is treated as a rigid body represented by a direction vector and the coordinates of its centre of mass. Constituent residues are mapped onto the helix axis in order to maintain the amino acid sequence dependent properties of helix. Helix packing is optimised according to a simple semi-empirical potential composed of three components: a helix-bilayer interaction potential, a helix crossing angle potential and a helix-helix distance potential. A Monte Carlo simulated annealing protocol is employed to optimise the helix bundle system, ie. to find low energy structures. A fortran program (TMH) has been developed to implement the method described.