Erk Subasi
Cagatay Basdogan*
College of Engineering
Koc University
Istanbul, 34450, Turkey
Presence, Vol. 17, No. 1, February 2008, 73–90
©
2008 by the Massachusetts Institute of Technology
A New Haptic Interaction and
Visualization Approach for Rigid
Molecular Docking in Virtual
Environments
Abstract
Many biological activities take place through the physicochemical interaction of two
molecules. This interaction occurs when one of the molecules finds a suitable loca-
tion on the surface of the other for binding. This process is known as molecular
docking, and it has applications to drug design. If we can determine which drug
molecule binds to a particular protein, and how the protein interacts with the
bonded molecule, we can possibly enhance or inhibit its activities. This information,
in turn, can be used to develop new drugs that are more effective against diseases.
In this paper, we propose a new approach based on a human-computer interaction
paradigm for the solution of the rigid body molecular docking problem. In our ap-
proach, a rigid ligand molecule (i.e., drug) manipulated by the user is inserted into
the cavities of a rigid protein molecule to search for the binding cavity, while the
molecular interaction forces are conveyed to the user via a haptic device for guid-
ance. We developed a new visualization concept, Active Haptic Workspace (AHW),
for the efficient exploration of the large protein surface in high resolution using a
haptic device having a small workspace. After the discovery of the true binding site
and the rough alignment of the ligand molecule inside the cavity by the user, its
final configuration is calculated off-line through time stepping molecular dynamics
(MD) simulations. At each time step, the optimum rigid body transformations of
the ligand molecule are calculated using a new approach, which minimizes the dis-
tance error between the previous rigid body coordinates of its atoms and their
new coordinates calculated by the MD simulations. The simulations are continued
until the ligand molecule arrives at the lowest energy configuration. Our experimen-
tal studies conducted with six human subjects testing six different molecular com-
plexes demonstrate that given a ligand molecule and five potential binding sites on
a protein surface, the subjects can successfully identify the true binding site using
visual and haptic cues. Moreover, they can roughly align the ligand molecule inside
the binding cavity such that the final configuration of the ligand molecule can be
determined via the proposed MD simulations.
*Correspondence to cbasdogan@ku.edu.tr.
Subasi and Basdogan 73