Improved NOE fitting for flexible molecules based on molecular mechanics data – a case study with S-adenosylmethionine
The use of molecular dynamics (MD) calculations to derive relative populations of conformers is highly sensitive to both timescale and parameterisation of the MD. Where these calculations are coupled with NOE data to determine the dynamics of a molecular system, this can present issues if these popu...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Royal Society of Chemistry
2018
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| Online Access: | https://eprints.nottingham.ac.uk/50105/ |
| _version_ | 1848798155492032512 |
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| author | Bame, Jessica Hoeck, Casper Carrington, Matthew J. Butts, Craig P. Jäger, Christof M. Croft, Anna K. |
| author_facet | Bame, Jessica Hoeck, Casper Carrington, Matthew J. Butts, Craig P. Jäger, Christof M. Croft, Anna K. |
| author_sort | Bame, Jessica |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | The use of molecular dynamics (MD) calculations to derive relative populations of conformers is highly sensitive to both timescale and parameterisation of the MD. Where these calculations are coupled with NOE data to determine the dynamics of a molecular system, this can present issues if these populations are thus relied upon. We present an approach that refines the highly accurate PANIC NMR methodology combined with clustering approaches to generate conformers, but without restraining the simulations or considering the relative population distributions generated by MD. Combining this structural sampling with NOE fitting, we demonstrate, for S-adenosylmethionine (aqueous solution at pH 7.0), significant improvements are made to the fit of populations to the experimental data, revealing a strong overall preference for the syn conformation of the adenosyl group relative to the ribose ring, but with less discrimination for the conformation of the ribose ring itself. |
| first_indexed | 2025-11-14T20:15:17Z |
| format | Article |
| id | nottingham-50105 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T20:15:17Z |
| publishDate | 2018 |
| publisher | Royal Society of Chemistry |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-501052019-02-23T04:30:13Z https://eprints.nottingham.ac.uk/50105/ Improved NOE fitting for flexible molecules based on molecular mechanics data – a case study with S-adenosylmethionine Bame, Jessica Hoeck, Casper Carrington, Matthew J. Butts, Craig P. Jäger, Christof M. Croft, Anna K. The use of molecular dynamics (MD) calculations to derive relative populations of conformers is highly sensitive to both timescale and parameterisation of the MD. Where these calculations are coupled with NOE data to determine the dynamics of a molecular system, this can present issues if these populations are thus relied upon. We present an approach that refines the highly accurate PANIC NMR methodology combined with clustering approaches to generate conformers, but without restraining the simulations or considering the relative population distributions generated by MD. Combining this structural sampling with NOE fitting, we demonstrate, for S-adenosylmethionine (aqueous solution at pH 7.0), significant improvements are made to the fit of populations to the experimental data, revealing a strong overall preference for the syn conformation of the adenosyl group relative to the ribose ring, but with less discrimination for the conformation of the ribose ring itself. Royal Society of Chemistry 2018-03-11 Article PeerReviewed application/pdf en https://eprints.nottingham.ac.uk/50105/1/c7cp07265a.pdf Bame, Jessica, Hoeck, Casper, Carrington, Matthew J., Butts, Craig P., Jäger, Christof M. and Croft, Anna K. (2018) Improved NOE fitting for flexible molecules based on molecular mechanics data – a case study with S-adenosylmethionine. Physical Chemistry Chemical Physics, 11 (20). pp. 7523-7531. ISSN 1463-9076 http://pubs.rsc.org/en/Content/ArticleLanding/2018/CP/C7CP07265A#!divAbstract doi:10.1039/C7CP07265A doi:10.1039/C7CP07265A |
| spellingShingle | Bame, Jessica Hoeck, Casper Carrington, Matthew J. Butts, Craig P. Jäger, Christof M. Croft, Anna K. Improved NOE fitting for flexible molecules based on molecular mechanics data – a case study with S-adenosylmethionine |
| title | Improved NOE fitting for flexible molecules based on molecular mechanics data – a case study with S-adenosylmethionine |
| title_full | Improved NOE fitting for flexible molecules based on molecular mechanics data – a case study with S-adenosylmethionine |
| title_fullStr | Improved NOE fitting for flexible molecules based on molecular mechanics data – a case study with S-adenosylmethionine |
| title_full_unstemmed | Improved NOE fitting for flexible molecules based on molecular mechanics data – a case study with S-adenosylmethionine |
| title_short | Improved NOE fitting for flexible molecules based on molecular mechanics data – a case study with S-adenosylmethionine |
| title_sort | improved noe fitting for flexible molecules based on molecular mechanics data – a case study with s-adenosylmethionine |
| url | https://eprints.nottingham.ac.uk/50105/ https://eprints.nottingham.ac.uk/50105/ https://eprints.nottingham.ac.uk/50105/ |