Direct fitting of structure and chemical shift to NMR spectra

Abstract

The possibility of determining protein structure directly from NMR spectra is investigated. Optimisation of four variables per atom (δ, x, y, z) directly against the nuclear Overhauser effect (NOE) spectrum by simulated annealing is shown to succeed in finding sets of coordinates (i.e. structures) and chemical shifts that match the reference configuration. The procedure is shown to work on both a fully resolved spectrum and when two resonances are overlapping. It is proposed that a direct approach may ultimately replace current methods of structure determination (assignment followed by structure calculation).