A robust algorithm for optimizing protein structures with NMR chemical shifts

Journal of Biomolecular NMR
Mark BerjanskiiDavid S Wishart

Abstract

Over the past decade, a number of methods have been developed to determine the approximate structure of proteins using minimal NMR experimental information such as chemical shifts alone, sparse NOEs alone or a combination of comparative modeling data and chemical shifts. However, there have been relatively few methods that allow these approximate models to be substantively refined or improved using the available NMR chemical shift data. Here, we present a novel method, called Chemical Shift driven Genetic Algorithm for biased Molecular Dynamics (CS-GAMDy), for the robust optimization of protein structures using experimental NMR chemical shifts. The method incorporates knowledge-based scoring functions and structural information derived from NMR chemical shifts via a unique combination of multi-objective MD biasing, a genetic algorithm, and the widely used XPLOR molecular modelling language. Using this approach, we demonstrate that CS-GAMDy is able to refine and/or fold models that are as much as 10 Å (RMSD) away from the correct structure using only NMR chemical shift data. CS-GAMDy is also able to refine of a wide range of approximate or mildly erroneous protein structures to more closely match the known/correct structure and ...Continue Reading

References

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May 2, 2009·Nucleic Acids Research·Mark BerjanskiiDavid S Wishart
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Mar 31, 2011·Journal of Biomolecular NMR·Beomsoo HanDavid S Wishart
Jun 6, 2012·Proceedings of the National Academy of Sciences of the United States of America·James M ThompsonDavid Baker
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Jun 15, 2015·Journal of Biomolecular NMR·Antonio RosatoGeerten W Vuister

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Citations

Apr 26, 2016·Chemical Reviews·Stephen Boulton, Giuseppe Melacini
Nov 10, 2017·Journal of Biomolecular NMR·Máximo Sanz-Hernández, Alfonso De Simone
Dec 3, 2017·Journal of Biomolecular NMR·Noor E HafsaDavid S Wishart
Mar 28, 2018·The Journal of Physical Chemistry. B·Justin L MacCallumKari Gaalswyk

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