Rigid Molecular Docking in Virtual Environments with Haptic Feedback

In this thesis, we present computationally efficient methods for visualization and simulation of molecular interactions in virtual environments with haptic feedback. In our simulations, the haptic device is used to guide a rigid ligand molecule into a receptor site while the molecular forces acting on the ligand molecule are scaled and reflected to the user in real-time. We demonstrate that the presence of a haptic interface accelerates the binding process and reduce the binding errors if it is used as a precursor to estimate the initial configuration of the ligand molecule at the binding site. After placement and rough alignment of the ligand molecule inside the binding cavity with the help of a haptic device, we use a novel computational approach to determine the final binding configuration of the ligand molecule. In this approach, the ligand molecule is treated as a rigid body seeking for the lowest potential energy configuration. The rigid body configurations of the ligand molecule is calculated in a least square sense using the new positions of its atoms moving under the influence of molecular interaction forces. The proposed approach is computationally more efficient than the molecular simulation methods that utilize the standard rigid-body formulations. We also present new methods for haptic visualization of a protein surface interactively to search for potential binding sites. Our experimental studies with 6 subjects show that subjects can successfully identify the true binding site among the 5 potential binding sites using visual and haptic cues. In addition, we show that the proposed distance minimization approach can be used to find the final configuration of a ligand molecule inside the binding cavity after it is initially aligned by the subject.