Patent ID: 6882939
Filing Date: 2005-04-19
Classification: G01N,G01R

Abstract:
1. A method for determining the global fold of a peptidic molecule having a sequence of three or greater amino acids which comprises the steps of: (a) providing said molecule in a form which is substituted on the backbone with an isotope selected from the group consisting of (b) subjecting said substituted molecule to NMR analysis in a non-aligned medium; (c) assigning said molecule by computer based on said NMR analysis; (d) placing said molecule in a first state of partial alignment and measuring residual dipolar couplings for said molecule in said first state of partial alignment, wherein the magnitudes and orientations of the principle axes of the alignment tensors for said first state of partial alignment are known or obtained; (e) placing said molecule in a second state of partial alignment and measuring residual dipolar couplings for said molecule in said second state of partial alignment, wherein the magnitudes and orientations of the principle axes of the alignment tensors for said second state of partial alignment are known or obtained; (f) varying computationally by increments the φ, ψ angles for a first amino acid of said molecule; (g) minimizing the rigid-body orientation of said first amino acid and a second amino acid adjacent in the peptidic sequence to said first amino acid with respect to both tensor frames simultaneously; (h) calculating the minimum difference between measured and calculated dipolar couplings for each of said first and second amino acids; (i) deriving the φ, ψ angles and orientation of the dipeptide fragment composed of said first and second amino acids; and (j) repeating steps (f)-(i) for each sequential dipeptide fragment of said molecule to obtain a global fold of said peptidic molecule.