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Building native protein conformation from NMR backbone chemical shifts using Monte Carlo fragment assembly
Author(s) -
Gong Haipeng,
Shen Yang,
Rose George D.
Publication year - 2007
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.072988407
Subject(s) - chemical shift , monte carlo method , steric effects , chemistry , cluster (spacecraft) , torsion (gastropod) , solvent , crystallography , nuclear magnetic resonance spectroscopy , hydrogen bond , molecule , chemical physics , topology (electrical circuits) , computational chemistry , stereochemistry , computer science , mathematics , organic chemistry , combinatorics , medicine , statistics , surgery , programming language
We have been analyzing the extent to which protein secondary structure determines protein tertiary structure in simple protein folds. An earlier paper demonstrated that three‐dimensional structure can be obtained successfully using only highly approximate backbone torsion angles for every residue. Here, the initial information is further diluted by introducing a realistic degree of experimental uncertainty into this process. In particular, we tackle the practical problem of determining three‐dimensional structure solely from backbone chemical shifts, which can be measured directly by NMR and are known to be correlated with a protein's backbone torsion angles. Extending our previous algorithm to incorporate these experimentally determined data, clusters of structures compatible with the experimentally determined chemical shifts were generated by fragment assembly Monte Carlo. The cluster that corresponds to the native conformation was then identified based on four energy terms: steric clash, solvent‐squeezing, hydrogen‐bonding, and hydrophobic contact. Currently, the method has been applied successfully to five small proteins with simple topology. Although still under development, this approach offers promise for high‐throughput NMR structure determination.