Protein structure determination by conformational space annealing using NMR geometric restraints

Keehyoung Joo, Insuk Joung, Jinhyuk Lee, Jinwoo Lee, Weon Tae Lee, Bernard Brooks, Sung Jong Lee, Jooyoung Lee

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We have carried out numerical experiments to investigate the applicability of the global optimization method of conformational space annealing (CSA) to the enhanced NMR protein structure determination over existing PDB structures. The NMR protein structure determination is driven by the optimization of collective multiple restraints arising from experimental data and the basic stereochemical properties of a protein-like molecule. By rigorous and straightforward application of CSA to the identical NMR experimental data used to generate existing PDB structures, we redetermined 56 recent PDB protein structures starting from fully randomized structures. The quality of CSA-generated structures and existing PDB structures were assessed by multiobjective functions in terms of their consistencies with experimental data and the requirements of protein-like stereochemistry. In 54 out of 56 cases, CSA-generated structures were better than existing PDB structures in the Pareto-dominant manner, while in the remaining two cases, it was a tie with mixed results. As a whole, all structural features tested improved in a statistically meaningful manner. The most improved feature was the Ramachandran favored portion of backbone torsion angles with about 8.6% improvement from 88.9% to 97.5% (P-value <10 -17 ). We show that by straightforward application of CSA to the efficient global optimization of an energy function, NMR structures will be of better quality than existing PDB structures.

Original languageEnglish
Pages (from-to)2251-2262
Number of pages12
JournalProteins: Structure, Function and Bioinformatics
Volume83
Issue number12
DOIs
Publication statusPublished - 2015 Dec 1

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Nuclear magnetic resonance
Annealing
Global optimization
Proteins
Stereochemistry
Torsional stress
Molecules
Experiments

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Cite this

Joo, Keehyoung ; Joung, Insuk ; Lee, Jinhyuk ; Lee, Jinwoo ; Lee, Weon Tae ; Brooks, Bernard ; Lee, Sung Jong ; Lee, Jooyoung. / Protein structure determination by conformational space annealing using NMR geometric restraints. In: Proteins: Structure, Function and Bioinformatics. 2015 ; Vol. 83, No. 12. pp. 2251-2262.
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Protein structure determination by conformational space annealing using NMR geometric restraints. / Joo, Keehyoung; Joung, Insuk; Lee, Jinhyuk; Lee, Jinwoo; Lee, Weon Tae; Brooks, Bernard; Lee, Sung Jong; Lee, Jooyoung.

In: Proteins: Structure, Function and Bioinformatics, Vol. 83, No. 12, 01.12.2015, p. 2251-2262.

Research output: Contribution to journalArticle

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