More specifically, we are developing a new computational approach and software package MIMIC that includes three main programs (Thread, Adjust, and Assembl) for the reliable automated modeling of TM alpha-helical domains, particularly, in G-protein coupled receptors (GPCR) and ABC transporters. The proposed method includes:
(1) generation of initial models of the TM domains by threading target amino acid sequences through the existing MsbA, BtuCD and rhodopsin structural templates (program Thread) and verification of the models using available experimental data;
(2) refinement of the models by optimizing spatial positions of TM helices and their kink angles with Adjust;
(3) docking two alpha-helical TM domains with Assembl program to reproduce the dimerization of ABC transporters and GPCR.

All our modeling software is based on all-atom free energy functions that have been derived recently from a large set of ΔΔG data for protein mutants [Lomize et al., 2002]. The developed method and software will be tested for proteins of known 3D structure, and then applied for large-scale modeling of transmembrane domains.