Associate Professor
Office Location: UH 263
Phone Number: (262) 472-5123
Email Address: traoreh@uww.edu
Research Interests
Research on Cannabinoids
Introduction:
My primary research interest is drug design. The initial step in drug design is the development of an understanding of how molecular structure relates to pharmacological activity. By varying a single substituent at a time, one can determine which aspects of the structure most influence its pharmacological activity. This information can be used to develop a more potent/selective compound.
The relationship between activity and structure results from molecular interaction at the site of action. If a compound's effect results from an interaction with a macromolecule such as an enzyme or receptor protein, both the shape and the electrostatics of the compound will be important. First, compounds must be able to adopt a receptor or enzyme appropriate conformation in order to fit in the receptor binding pocket or enzyme active site. The positioning of key functional groups for intermolecular interactions between receptor/enzyme and compound is then key. The greater the intermolecular forces (such as hydrogen bonding and van der Waal's inetractions), the more tightly bound will be the compound at the site. Because the conformation of a molecule affects its shape and its ability to place key functional groups for interaction at a site, conformation analysis and conformational memories are the first steps in understanding the relationship between structure and activity.
Primary objective:
The primary objective of our research is to use computational modeling supported by experimental studies to explore the relationships between cannabinoid ligand and cannabinoid receptor activity at an atomic level of detail. The model system we are interested in is structural well characterized CB1 receptor and cannabinoid ligands. Our research plan is organized around two emphases:
- Ligand-Ligand Studies:
In these studies we focus we will infer information about macromolecular binding site (e.g CB receptors and modes of binding interactions at these receptors) from a correlation between experimentally determined receptor affinities and biological activities and structural and electronic features of a series of cannabinoid ligands.
- Ligand-Receptor Studies:
In these studies we focus not only on elements recognition at the CB receptor but
also on the consequences of ligand binding.
Methodology:
The methodology used in my research includes the full gamut of small molecule modeling techniques. These include ab-initio, semi-empirical, molecular mechanics, conformational studies of ligands, as well as (for highly flexible ligands) conformational memories studies. Macromolecule modeling techniques used include standard protein structure refinement techniques such as Amber; molecular dynamics calculations to stimulate time dependent behavior of the macromolecule, as well as, Monte Carlo/Stochastic Dynamics Techniques to explore more completely the conformational space of the macromolecule. The scope and objectives of our research go beyond study of ligand-ligand studies and ligand-receptor studies. The methodology proposed here has applications to a wide spectrum of problems in molecular recognition ranging from drug-receptor interaction to drug design.
Research in Green Chemistry
Another interest we are developing is in Green Chemistry.