Distance-constraint pseudoenergies

Structural solution obtained by minimization in the absence of distance constraint pseudoenergies. One state structural solution obtained by minimization with distance constraint pseudoenergies. Two state structural solution obtained by minimization with distance constraint pseudoenergies. 

The basis for the determination of solution conformation from NMR data lies in the determination of cross relaxation rates between pairs of protons from cross peak intensities in two-dimensional nuclear Overhauser effect (NOE) experiments. In the event that pairs of protons may be assumed to be rigidly fixed in an isotopically tumbling sphere, a simple inverse sixth power relationship between interproton distances and cross relaxation rates permits the accurate determination of distances. Determination of a sufficient number of interproton distance constraints can lead to the unambiguous determination of solution conformation, as illustrated in the early work of Kuntz, et al. (25). While distance geometry algorithms remain the basis of much structural work done today (1-4), other approaches exist. For instance, those we intend to apply here represent NMR constraints as pseudoenergies for use in molecular dynamics or molecular mechanics programs (5-9). 

In order to incorporate distance constraints derived from two-dimensional crossrelaxation data in a molecular mechanics program, we have chosen to treat the constraints as a pseudoenergy function. This function should ideally reflect the distance dependence of cross relaxation rates. Previously, we had proposed a function of the form (40) ... 

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