Visual and Force Feedback-enabled Docking for Rational Drug Design

Transmembrane helices play basic roles in biology: signal transduction, ion transport and protein folding. While antibodies can be directed towards hydrophilic regions of molecules, transmembrane regions have not been targeted so far. In this paper, we propose a novel approach to search for helix-helix complementary pairs in order to inhibit, or modulate, the function of membrane proteins where point mutations at the transmembrane domain have been found to lead to various forms of cancer such as the homodimeric epidermal, or fibroblast, growth factor receptors. This method employs visual and force feedback tools to search for the optimal interaction between helices. The search is manual, exploring helix tilt, helix rotation and side chain rotamer selection, with feedback from the models consisting of a repulsion or attraction force. We developed a prototype system that allows real-time interactive visualization and manipulation of molecules with force feedback in virtual environment. In our system, we implemented haptic interface to facilitate the exploration and analysis of molecular docking. Haptic device enables the user to manipulate the molecules and feel its interaction during the docking process in virtual experiment on computer. In future, these techniques could help the user to understand molecular interactions, and to evaluate the design of pharmaceutical drugs.