Abstract

The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the Pennsylvania Department of Health, or of any Motivation: High-throughput structural proteomics requires fast robust algorithms for extracting protein structure from sparse experimental data. Current approaches are too slow. Determining the 3D structure of an unknown protein may require 6–12 months, mainly for data interpretation. Determining ligand induced changes in structure of a previously known protein may still require weeks of effort. This second problem is of great interest to drug designers, and is our main focus in this paper. A key step is the resonance assignment problem, in which observed NMR peaks must be matched to a protein’s atoms. Contributions: This paper describes two novel procedures, together called PEPMORPH, for inferring structure and assigning resonances: (1) A method for extracting combinatorial protein substructures directly from sparse NMR experiments; (2) A method for matching experimental to known substructures by exploiting the orientational constraint of residual dipolar coupling (RDC). PEPMORPH reverses the traditional approach, in which NMR resonances are assigned prior to

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