During the course of biological function, proteins interact with other proteins, ligands, substrates, inhibitors, etc. These interactions occur at precisely defined locations with the protein but their effects are sometimes propagated to distal regions triggering highly specific responses. These effects can be used as signals directed to activate or inhibit other sites, modulate interactions with other molecules and /or establish inter-molecular communication networks. It has become evident hat the energy of stabilization of the protein structure is not evenly distributed throughout the molecule and that, under native conditions, proteins lack global cooperativeness and are characterized by the occurrence of multiple independent local unfolding events. It is important to assess if this uneven distribution reflects specific functional requirements.
Technical Details:
Johns Hopkins University is looking for a partner to market a novel method for tracing the path of a ligand binding signal through the three-dimensional structure of a macromolecule by determining the stability of the residues of the macromolecule in the presence and absence of the ligand. The method provides a computer-assisted method for creating and displaying a model of a molecule in which residues that are affected by the binding of a ligand to the molecule are highlighted, making it possible to trace the path of propagation of a binding signal through the molecule. In order to carry out the method, the binding site determinants of the molecule are determined and the binding constant for the ligand is calculated. The states of a conformational ensemble that are binding competent are identified, and the Gibbs energy and probability of each state and the stability constant per residue of the molecule are calculated in the presence and absence of the ligand. Those residues that display a difference in stability constant in the presence vs. absence of ligand are those, which are affected by the binding of the ligand.
Looking for Partners:
New drug development and design, predictive analysis of ligand binding
