Kinetic rate constant prediction supports the conformational selection mechanism of protein binding.
The prediction of protein-protein kinetic rate constants provides a fundamental test of our understanding of molecular recognition, and will play an important role in the modeling of complex biological systems. In this paper, a feature selection and regression algorithm is applied to mine a large se...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1002351&type=printable |
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| _version_ | 1849331172044177408 |
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| author | Iain H Moal Paul A Bates |
| author_facet | Iain H Moal Paul A Bates |
| author_sort | Iain H Moal |
| collection | DOAJ |
| description | The prediction of protein-protein kinetic rate constants provides a fundamental test of our understanding of molecular recognition, and will play an important role in the modeling of complex biological systems. In this paper, a feature selection and regression algorithm is applied to mine a large set of molecular descriptors and construct simple models for association and dissociation rate constants using empirical data. Using separate test data for validation, the predicted rate constants can be combined to calculate binding affinity with accuracy matching that of state of the art empirical free energy functions. The models show that the rate of association is linearly related to the proportion of unbound proteins in the bound conformational ensemble relative to the unbound conformational ensemble, indicating that the binding partners must adopt a geometry near to that of the bound prior to binding. Mirroring the conformational selection and population shift mechanism of protein binding, the models provide a strong separate line of evidence for the preponderance of this mechanism in protein-protein binding, complementing structural and theoretical studies. |
| format | Article |
| id | doaj-art-a8786f26916b44508a7fd1d5e5ec6d93 |
| institution | Kabale University |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-a8786f26916b44508a7fd1d5e5ec6d932025-08-20T03:46:42ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582012-01-0181e100235110.1371/journal.pcbi.1002351Kinetic rate constant prediction supports the conformational selection mechanism of protein binding.Iain H MoalPaul A BatesThe prediction of protein-protein kinetic rate constants provides a fundamental test of our understanding of molecular recognition, and will play an important role in the modeling of complex biological systems. In this paper, a feature selection and regression algorithm is applied to mine a large set of molecular descriptors and construct simple models for association and dissociation rate constants using empirical data. Using separate test data for validation, the predicted rate constants can be combined to calculate binding affinity with accuracy matching that of state of the art empirical free energy functions. The models show that the rate of association is linearly related to the proportion of unbound proteins in the bound conformational ensemble relative to the unbound conformational ensemble, indicating that the binding partners must adopt a geometry near to that of the bound prior to binding. Mirroring the conformational selection and population shift mechanism of protein binding, the models provide a strong separate line of evidence for the preponderance of this mechanism in protein-protein binding, complementing structural and theoretical studies.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1002351&type=printable |
| spellingShingle | Iain H Moal Paul A Bates Kinetic rate constant prediction supports the conformational selection mechanism of protein binding. PLoS Computational Biology |
| title | Kinetic rate constant prediction supports the conformational selection mechanism of protein binding. |
| title_full | Kinetic rate constant prediction supports the conformational selection mechanism of protein binding. |
| title_fullStr | Kinetic rate constant prediction supports the conformational selection mechanism of protein binding. |
| title_full_unstemmed | Kinetic rate constant prediction supports the conformational selection mechanism of protein binding. |
| title_short | Kinetic rate constant prediction supports the conformational selection mechanism of protein binding. |
| title_sort | kinetic rate constant prediction supports the conformational selection mechanism of protein binding |
| url | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1002351&type=printable |
| work_keys_str_mv | AT iainhmoal kineticrateconstantpredictionsupportstheconformationalselectionmechanismofproteinbinding AT paulabates kineticrateconstantpredictionsupportstheconformationalselectionmechanismofproteinbinding |