Method of characterizing interactions and screening for effectors

Abstract

This invention enables high throughput detection of small molecule effectors of particle association, as well as quantification of association constants, stoichiometry, and conformation. 'Particle' refers to any discrete particle, such as a protein, nucleic acid, carbohydrate, liposome, virus, synthesized polymer, nanoparticle, colloid, latex sphere, etc. Given a set of particle solutions having different concentrations, dynamic light scattering measurements are used to determine the average hydrodynamic radius, r, as a function of concentration. The series of ras a function of concentration are fitted with stoichiometric association models containing the parameters of molar mass, modeled concentrations, and modeled hydrodynamic radii of the associated complexes. In addition to the rvalue analysis, the experimental data may be fit/analyzed in alternate ways. This method may be applied to a single species that is self-associating or to multiple species that are hetero-associating. This method may also be used to characterize and quantify the association between a modulator and the associating species.