Patent ID: 8504304

Claim:
A computer-implemented method of determining a preferred binding pose of a ligand in a complex comprising a target protein and a ligand using non-scalar magnetic couplings, comprising: (a) assigning the NMR resonance shifts of the ligand; (b) acquiring data from an observed NMR peak pattern comprising target protein resonances and ligand resonances using an NMR spectrometer, the peak pattern indicating non-scalar couplings between the nuclei of a sample comprising a target protein and a ligand, without requiring assignments for the NMR resonances of the target protein; (c) designating a set of three-dimensional, structural coordinates for one or more trial binding poses for at least a portion of the protein-ligand complex; (d) predicting an NMR peak pattern arising from non-scalar couplings between the target protein and the ligand in its designated trial binding pose, (e) finding the optimal match between the predicted peak pattern with the observed peak pattern using an equally partitioned bipartite weighted matching algorithm; (f) based on the match, assigning the trial binding pose a quantitative score representing the degree of similarity between the observed and predicted peak patterns; (g) repeating steps (c) through (f) a desired number of times to generate a quantitative score for each of one or more binding poses; and (h) evaluating the relative quantitative scores to identify one or more binding poses that are the most consistent with the observed peak pattern, wherein one or more of steps (a) through (h) are performed by a computer programmed to carry out each step.