APPLICATION OF METAHEURISTIC APPROACH TO MODEL AN ASSEMBLY OF TRANSMEMBRANE HELICAL BUNDLE IN INTEGRAL MEMBRANE PROTEINS

Despite the rapid growth of solved 3D structures proteins, a relatively low percentage of all structures of the Protein Data Bank is transmembrane proteins due to technical difficulties for high-resolution structure determination. This study proposes a novel algorithm. Max-Min Ant System, designed to find an assembly of α-helical transmembrane proteins using a rigid helix arrangement guided by distance constraints. The method called THAMMAS (Transmembrane Helix Assembly by Max-Min Ant System) generates a variety of orientations of transmembrane helix bundle and finds the solution that is matched with the provided distance constraints based on the behavior of ants to search for the shortest possible path between their nest and the food source. To demonstrate the efficiency of the novel algorithm, THAMMAS are applied to determine the transmembrane packing of KcsA and MscL ion channels from distance information extracted from the crystal structures, and the packing of KvAP voltage sensor domain using a set of experimentally-determined constraints and the results are compared with those of conventional optimization algorithms, Simulated Annealing Monte Carlo method and Genetic Algorithm.