A. Yu. Rogachev
Illinois Institute of Technology,
Keywords: drug design, modeling
Summary:In this talk, I will present our new direction, in which we apply all our experience and skills in theoretical chemistry to resolve one of the main problem of modern pharmaceutical and medicinal chemistry – directed design of desired drug(s). Instead of screening huge libraries of potential candidates, we propose an approach that will allow one to specifically design the drug molecule with pronounced and maximized important properties (in our specific case – antagonist behavior) and minimized or even eliminated side effects (for instance, addiction). Nowadays, the field is exclusively dominated by computational approaches, which have docking procedure of screening of huge libraries of potential candidates at the heart of the engine. In spite of providing reasonable and important information about binding constant, these methods are strictly deficient in identification of exact type of non-covalent interactions between small drug molecule and receptor, thus skipping a huge amount of critically important information. In the our research, we utilize fundamentally different approach, based on accurate theoretical evaluation of the type and energetics of all weak non-covalent interactions. The ultimate goal is to construct the complete map of weak interactions between small drug molecule and receptor in target systems. Once successful, it will lead to deep understanding the difference between, for instance, agonists’ and antagonists’ behavior and, as a result, to design a specific molecule with desirable properties. Thus, instead of screening huge libraries with a little hope to find one unique molecule with desirable binding constant, we will be able to directly design such molecule. Once successful, it will potentially revolutionize the field of drug discovery.