Improving Coarse-Grained Protein Force Fields with Small-Angle X-ray Scattering Data
Small-angle X-ray scattering (SAXS) experiments provide valuable structural data for biomolecules in solution. We develop a highly efficient maximum entropy approach to fit SAXS data by introducing minimal biases to a coarse-grained protein force field, the associative memory, water mediated, struct...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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American Chemical Society (ACS)
2021
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| Online Access: | https://hdl.handle.net/1721.1/129455 |
| _version_ | 1811079734732259328 |
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| author | Latham, Andrew P Zhang, Bin |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Latham, Andrew P Zhang, Bin |
| author_sort | Latham, Andrew P |
| collection | MIT |
| description | Small-angle X-ray scattering (SAXS) experiments provide valuable structural data for biomolecules in solution. We develop a highly efficient maximum entropy approach to fit SAXS data by introducing minimal biases to a coarse-grained protein force field, the associative memory, water mediated, structure, and energy model (AWSEM). We demonstrate that the resulting force field, AWSEM-SAXS, succeeds in reproducing scattering profiles and models protein structures with shapes that are in much better agreement with experimental results. Quantitative metrics further reveal a modest, but consistent, improvement in the accuracy of modeled structures when SAXS data are incorporated into the force field. Additionally, when applied to a multiconformational protein, we find that AWSEM-SAXS is able to recover the population of different protein conformations from SAXS data alone. We, therefore, conclude that the maximum entropy approach is effective in fine-tuning the force field to better characterize both protein structure and conformational fluctuation. |
| first_indexed | 2024-09-23T11:19:42Z |
| format | Article |
| id | mit-1721.1/129455 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:19:42Z |
| publishDate | 2021 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1294552022-10-01T02:53:05Z Improving Coarse-Grained Protein Force Fields with Small-Angle X-ray Scattering Data Latham, Andrew P Zhang, Bin Massachusetts Institute of Technology. Department of Chemistry Small-angle X-ray scattering (SAXS) experiments provide valuable structural data for biomolecules in solution. We develop a highly efficient maximum entropy approach to fit SAXS data by introducing minimal biases to a coarse-grained protein force field, the associative memory, water mediated, structure, and energy model (AWSEM). We demonstrate that the resulting force field, AWSEM-SAXS, succeeds in reproducing scattering profiles and models protein structures with shapes that are in much better agreement with experimental results. Quantitative metrics further reveal a modest, but consistent, improvement in the accuracy of modeled structures when SAXS data are incorporated into the force field. Additionally, when applied to a multiconformational protein, we find that AWSEM-SAXS is able to recover the population of different protein conformations from SAXS data alone. We, therefore, conclude that the maximum entropy approach is effective in fine-tuning the force field to better characterize both protein structure and conformational fluctuation. 2021-01-19T21:10:03Z 2021-01-19T21:10:03Z 2019-02 2020-10-14T16:43:24Z Article http://purl.org/eprint/type/JournalArticle 1520-6106 https://hdl.handle.net/1721.1/129455 Latham, Andrew P., and Bin Zhang. "Improving Coarse-Grained Protein Force Fields with Small-Angle X-ray Scattering Data." Journal of Physical Chemistry B 123, 5 (February 2019): 957-1214 doi 10.1021/ACS.JPCB.8B10336 ©2019 Author(s) en 10.1021/ACS.JPCB.8B10336 Journal of Physical Chemistry B Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) Prof. Zhang via Ye Li |
| spellingShingle | Latham, Andrew P Zhang, Bin Improving Coarse-Grained Protein Force Fields with Small-Angle X-ray Scattering Data |
| title | Improving Coarse-Grained Protein Force Fields with Small-Angle X-ray Scattering Data |
| title_full | Improving Coarse-Grained Protein Force Fields with Small-Angle X-ray Scattering Data |
| title_fullStr | Improving Coarse-Grained Protein Force Fields with Small-Angle X-ray Scattering Data |
| title_full_unstemmed | Improving Coarse-Grained Protein Force Fields with Small-Angle X-ray Scattering Data |
| title_short | Improving Coarse-Grained Protein Force Fields with Small-Angle X-ray Scattering Data |
| title_sort | improving coarse grained protein force fields with small angle x ray scattering data |
| url | https://hdl.handle.net/1721.1/129455 |
| work_keys_str_mv | AT lathamandrewp improvingcoarsegrainedproteinforcefieldswithsmallanglexrayscatteringdata AT zhangbin improvingcoarsegrainedproteinforcefieldswithsmallanglexrayscatteringdata |