Iterative procedure for structure determination from proton-proton NOEs using a full relaxation matrix approach. Application to a DNA octamer

Abstract

A method is proposed, called the iterative relaxation matrix approach (IRMA), for the structure determination of biomolecules in solution based on 2D NOE data. Proton-proton distances are determined in a way in which indirect magnetization transfer (spin diffusion) is taken fully into account. In this method experimental NOEs are combined with calculated NOE values based on a molecular model. Back-transformation of this mixed NOE matrix gives a relaxation matrix which provides a better estimation of 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 are used in restrained molecular dynamics calculations to obtain an improved molecular model. The iteration cycle can be repeated until all experimental NOE values are satisfactorily explained. The method was tested with a DNA octamer, d(GCGTTGCG)·d(CGCAACGC).