Complete Relaxation and Conformational Exchange Matrix (CORCEMA) Analysis of NOESY Spectra of Reversibly Forming Ligand-Receptor Complexes Application to Transferred NOESY

Complete Relaxation and Conformational Exchange Matrix (CORCEMA) Analysis of Intermolecular Saturation Transfer Effects in Reversibly Forming Ligand–Receptor Complexes

“…For methyl groups where the internal rotational correlation times can be considerably shorter than the overall rotational correlation time, a "model-free" calculation of spectral densities with order parameters (S 2 ) and internal (τ m ) and overall (τ r ) correlation times was used to calculate spectral densities involving intramethyl and methyl-to-other proton dipolar interactions, as in Refs. (7,8,(14)(15)(16). For intramethyl proton-proton interactions, S 2 was set to 0.25.…”

“…From Eq. [1] it is seen that for very small times after instantaneous saturation, the initial signal is given by [7] where H stands for higher order terms in the expansion. If the exchange is fast on both chemical shift and relaxation rate scales, a similar expression is obtained from Eq.…”

“…When the exchange is fast on the relaxation rate scale, it can be shown using the matrix algebra procedures for multistate kinetics of biomolecules developed by us previously (6,7,19) that an approximate solution to Eq. [1] is obtained (assuming fast exchange on the chemical shift scale),…”

“…[10]) gives the calculated intensities in the STD-NMR experiment using an exact CORCEMA treatment applicable over the entire range of exchange rates while Eq. [5] gives the CORCEMA calculated intensities using the "average relaxation rate matrix theory" (6,7,20) that is valid strictly only when the exchange rates are much larger than the relaxation rates. It is reasonable to ask under what conditions the predictions of Eq.…”

“…We have also assumed, for simplicity, that each molecular species in the above scheme undergoes simple isotropic rotational diffusion. Internal motions (in particular the methyl groups) are incorporated (7,8) by "model-free" calculations for spectral density in terms of order parameters, internal correlation times, and overall correlation times (14)(15)(16). We also assume that the receptor protons can be subdivided into two classes, E1 (and E1 ) and E2 (and E2 ), where E2 and E2 stand for protons that experience RF irradiation directly (e.g., aromatic ring protons, or some select CH 3 protons from some specified residues in the case of an STD-NMR, or aliphatic protons in the ICS-NMR).…”