Proteins in Mixed Solvents: A Molecular-level Perspective
We present a statistical mechanical approach for quantifying thermodynamic properties of proteins in mixed solvents. This approach, based on molecular dynamics simulations which incorporate all atom models and the theory of preferential binding, allows us to compute transfer free energies with exper...
| Main Authors: | , , |
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| Format: | Article |
| Language: | en_US |
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2003
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| Online Access: | http://hdl.handle.net/1721.1/3945 |
| _version_ | 1826201246282809344 |
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| author | Baynes, Brian M. Wang, Daniel I.C. Trout, Bernhardt L. |
| author_facet | Baynes, Brian M. Wang, Daniel I.C. Trout, Bernhardt L. |
| author_sort | Baynes, Brian M. |
| collection | MIT |
| description | We present a statistical mechanical approach for quantifying thermodynamic properties of proteins in mixed solvents. This approach, based on molecular dynamics simulations which incorporate all atom models and the theory of preferential binding, allows us to compute transfer free energies with experimental accuracy and does not incorporate any adjustable parameters. Specifically, we applied our approach to the model proteins RNase A and T1, and the solvent components water, glycerol, and urea. We found that the observed differences in the binding of glycerol and urea to RNase T1 and A are predominantly a consequence of density differences in the first coordination shell of the protein with the cosolvents, but the second solvation shell also contributes to the overall binding coefficients. The success of this approach in modeling preferential binding indicates that it incorporates the important underlying physics of proteins in mixed solvent systems and that the difficulty in quantitative prediction to date can be surmounted by explicitly incorporating the complex protein-solvent and solvent-solvent interactions. |
| first_indexed | 2024-09-23T11:49:00Z |
| format | Article |
| id | mit-1721.1/3945 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:49:00Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | mit-1721.1/39452019-04-10T08:59:16Z Proteins in Mixed Solvents: A Molecular-level Perspective Baynes, Brian M. Wang, Daniel I.C. Trout, Bernhardt L. glycerol molecular dynamics preferential binding ribonuclease urea We present a statistical mechanical approach for quantifying thermodynamic properties of proteins in mixed solvents. This approach, based on molecular dynamics simulations which incorporate all atom models and the theory of preferential binding, allows us to compute transfer free energies with experimental accuracy and does not incorporate any adjustable parameters. Specifically, we applied our approach to the model proteins RNase A and T1, and the solvent components water, glycerol, and urea. We found that the observed differences in the binding of glycerol and urea to RNase T1 and A are predominantly a consequence of density differences in the first coordination shell of the protein with the cosolvents, but the second solvation shell also contributes to the overall binding coefficients. The success of this approach in modeling preferential binding indicates that it incorporates the important underlying physics of proteins in mixed solvent systems and that the difficulty in quantitative prediction to date can be surmounted by explicitly incorporating the complex protein-solvent and solvent-solvent interactions. Singapore-MIT Alliance (SMA) 2003-12-16T14:16:47Z 2003-12-16T14:16:47Z 2004-01 Article http://hdl.handle.net/1721.1/3945 en_US Molecular Engineering of Biological and Chemical Systems (MEBCS); 2065249 bytes application/pdf application/pdf |
| spellingShingle | glycerol molecular dynamics preferential binding ribonuclease urea Baynes, Brian M. Wang, Daniel I.C. Trout, Bernhardt L. Proteins in Mixed Solvents: A Molecular-level Perspective |
| title | Proteins in Mixed Solvents: A Molecular-level Perspective |
| title_full | Proteins in Mixed Solvents: A Molecular-level Perspective |
| title_fullStr | Proteins in Mixed Solvents: A Molecular-level Perspective |
| title_full_unstemmed | Proteins in Mixed Solvents: A Molecular-level Perspective |
| title_short | Proteins in Mixed Solvents: A Molecular-level Perspective |
| title_sort | proteins in mixed solvents a molecular level perspective |
| topic | glycerol molecular dynamics preferential binding ribonuclease urea |
| url | http://hdl.handle.net/1721.1/3945 |
| work_keys_str_mv | AT baynesbrianm proteinsinmixedsolventsamolecularlevelperspective AT wangdanielic proteinsinmixedsolventsamolecularlevelperspective AT troutbernhardtl proteinsinmixedsolventsamolecularlevelperspective |