Computer Graphics in Real-time Docking with Energy Calculation and Minimization

We describe a real-time docking method using molecular graphics and high-speed calculation of the energy of interaction between a drug and a receptor. A three-dimensional tabulation of the potential is computed prior to the docking experiment, and the total interaction energy is calculated and updated on the display screen in real-time to provide immediate visual feedback to the user as the drug molecule is moved inside the receptor pocket. The "Simplex" method is then used to minimize the energy of interactions after each docking. Using this real-time method, it is now possible to examine rapidly the interactions of a large number of drugs and their analogues with receptor molecules. As an application, the interaction of thyroid hormone and its analogues with prealbumin is considered. The final interaction energies of this very rapid method compare well with those calculated by more orthodox means, while also providing visual feedback on both molecular geometry and energy.