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Statistical Analysis of Crystallization Database Links Protein Physico-Chemical Features with Crystallization Mechanisms

X-ray crystallography is the predominant method for obtaining atomic-scale information about biological macromolecules. Despite the success of the technique, obtaining well diffracting crystals still critically limits going from protein to structure. In practice, the crystallization process proceeds...

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Autores principales: Fusco, Diana, Barnum, Timothy J., Bruno, Andrew E., Luft, Joseph R., Snell, Edward H., Mukherjee, Sayan, Charbonneau, Patrick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079662/
https://www.ncbi.nlm.nih.gov/pubmed/24988076
http://dx.doi.org/10.1371/journal.pone.0101123
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author Fusco, Diana
Barnum, Timothy J.
Bruno, Andrew E.
Luft, Joseph R.
Snell, Edward H.
Mukherjee, Sayan
Charbonneau, Patrick
author_facet Fusco, Diana
Barnum, Timothy J.
Bruno, Andrew E.
Luft, Joseph R.
Snell, Edward H.
Mukherjee, Sayan
Charbonneau, Patrick
author_sort Fusco, Diana
collection PubMed
description X-ray crystallography is the predominant method for obtaining atomic-scale information about biological macromolecules. Despite the success of the technique, obtaining well diffracting crystals still critically limits going from protein to structure. In practice, the crystallization process proceeds through knowledge-informed empiricism. Better physico-chemical understanding remains elusive because of the large number of variables involved, hence little guidance is available to systematically identify solution conditions that promote crystallization. To help determine relationships between macromolecular properties and their crystallization propensity, we have trained statistical models on samples for 182 proteins supplied by the Northeast Structural Genomics consortium. Gaussian processes, which capture trends beyond the reach of linear statistical models, distinguish between two main physico-chemical mechanisms driving crystallization. One is characterized by low levels of side chain entropy and has been extensively reported in the literature. The other identifies specific electrostatic interactions not previously described in the crystallization context. Because evidence for two distinct mechanisms can be gleaned both from crystal contacts and from solution conditions leading to successful crystallization, the model offers future avenues for optimizing crystallization screens based on partial structural information. The availability of crystallization data coupled with structural outcomes analyzed through state-of-the-art statistical models may thus guide macromolecular crystallization toward a more rational basis.
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spelling pubmed-40796622014-07-08 Statistical Analysis of Crystallization Database Links Protein Physico-Chemical Features with Crystallization Mechanisms Fusco, Diana Barnum, Timothy J. Bruno, Andrew E. Luft, Joseph R. Snell, Edward H. Mukherjee, Sayan Charbonneau, Patrick PLoS One Research Article X-ray crystallography is the predominant method for obtaining atomic-scale information about biological macromolecules. Despite the success of the technique, obtaining well diffracting crystals still critically limits going from protein to structure. In practice, the crystallization process proceeds through knowledge-informed empiricism. Better physico-chemical understanding remains elusive because of the large number of variables involved, hence little guidance is available to systematically identify solution conditions that promote crystallization. To help determine relationships between macromolecular properties and their crystallization propensity, we have trained statistical models on samples for 182 proteins supplied by the Northeast Structural Genomics consortium. Gaussian processes, which capture trends beyond the reach of linear statistical models, distinguish between two main physico-chemical mechanisms driving crystallization. One is characterized by low levels of side chain entropy and has been extensively reported in the literature. The other identifies specific electrostatic interactions not previously described in the crystallization context. Because evidence for two distinct mechanisms can be gleaned both from crystal contacts and from solution conditions leading to successful crystallization, the model offers future avenues for optimizing crystallization screens based on partial structural information. The availability of crystallization data coupled with structural outcomes analyzed through state-of-the-art statistical models may thus guide macromolecular crystallization toward a more rational basis. Public Library of Science 2014-07-02 /pmc/articles/PMC4079662/ /pubmed/24988076 http://dx.doi.org/10.1371/journal.pone.0101123 Text en © 2014 Fusco et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Fusco, Diana
Barnum, Timothy J.
Bruno, Andrew E.
Luft, Joseph R.
Snell, Edward H.
Mukherjee, Sayan
Charbonneau, Patrick
Statistical Analysis of Crystallization Database Links Protein Physico-Chemical Features with Crystallization Mechanisms
title Statistical Analysis of Crystallization Database Links Protein Physico-Chemical Features with Crystallization Mechanisms
title_full Statistical Analysis of Crystallization Database Links Protein Physico-Chemical Features with Crystallization Mechanisms
title_fullStr Statistical Analysis of Crystallization Database Links Protein Physico-Chemical Features with Crystallization Mechanisms
title_full_unstemmed Statistical Analysis of Crystallization Database Links Protein Physico-Chemical Features with Crystallization Mechanisms
title_short Statistical Analysis of Crystallization Database Links Protein Physico-Chemical Features with Crystallization Mechanisms
title_sort statistical analysis of crystallization database links protein physico-chemical features with crystallization mechanisms
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079662/
https://www.ncbi.nlm.nih.gov/pubmed/24988076
http://dx.doi.org/10.1371/journal.pone.0101123
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