Determination of biomolecular structures from proton-proton NOE's using a relaxation matrix approach

A method is proposed for the structure determination of biomolecules in solution based on 2D NOE data in which indirect magnetization transfer (spin diffusion) is taken into account. In this method experimental NOE's are supplemented with calculated NOE's based on a molecular model. Back transformation of this mixed NOE matrix gives a relaxation matrix which provides a better estimation for the cross-relaxation rates than can be obtained directly from the NOE cross-peaks. From the cross-relaxation rates distance constraints can be derived, which can be used in distance geometry and restrained molecular dynamics calculations to obtain an improved molecular model. The procedure can be repeated until all experimental NOE's are satisfactorily explained.