  The finely tuned structures of membrane channels allow selective passage of
ions through the available aqueous pores. In order to understand channel
function, it is crucial to locate the pore and study its physical and chemical
properties. Recently obtained X-ray crystal structures of bacterial chloride
channel homologues reveal a complicated topology with curvilinear pores. The
commonly used HOLE program encounters difficulties in studying such pores. Here
we propose a new pore-searching algorithm (TransPath) which uses the
Configurational Bias Monte Carlo (CBMC) method to generate transmembrane
trajectories driven by both geometric and electrostatic features. The
trajectories are binned into groups determined by a vector distance criterion.
  From each group, a representative trajectory is selected based on the
Rosenbluth weight, and the geometrically optimal path is obtained by simulated
annealing. Candidate ion pathways can then be determined by analysis of the
radius and potential profiles. The proposed method and its implementation are
illustrated using the bacterial KcsA potassium channel as an example. The
procedure is then applied to the more complex structures of the bacterial E.
coli ClC channel homologues.
