Medicinal Chemistry

Scientists at the Merck Frosst Centre for Therapeutic Research use computational simulation methods to speed up the process of producing compounds with desirable properties. Molecules can be designed and visualized on a computer screen and docked into the active site on a virtual enzyme, before the real compound is made. This strong predictive ability has prompted considerable interest in the technique, and it is now applied routinely in other programs.

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Computational chemists at Merck Frosst draw from an extensive database of small molecules, both real and virtual, to find candidates for specific biologic targets. They apply force field and electronic structure calculations to small molecules to determine molecular properties such as energies, geometries and reactivities.

Structure-based design studies are based on experimentally determined protein structures for the therapeutic target. These studies apply force field methods such as the Merck Molecular Force Field ( MMFF^® ) and AMBER ^® to molecular dynamics and free-energy calculations on explicitly solvated systems, as well as conventional gas-phase minimizations.

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When the structure of the therapeutic target is not known, more abstract methods such as similarity/dissimilarity searching and pharmacophore mapping can be applied. A wide variety of these computational methods have been advanced within Merck Research Laboratories worldwide, building a strong base of state-of-the-art computational chemistry tools together with the associated expertise within the company as a whole. In addition to a 24-processor SGI™ Origin™ and a 32-processor IBM™ Regatta™ on site, high performance computing facilities on other Merck sites worldwide are transparently accessible. Using these advanced computational methods together with the experimental biology and medicinal chemistry to validate hypotheses makes a powerful combination, placing Merck Frosst Canada Ltd. at the forefront in drug design.

® Registered Trademark of Merck & Co., Inc. Used under license.
MMFF® is a property of Merck & Co., Inc
AMBER® is a registered trademark of Regents of the University of California, 1984-2000.
™ SGI and Origin2000 are trademarks of Silicon Graphics, Inc.
™ IBM and Regatta are trademarks of International Business Machines Corporation.