Cooperativity in Binding Processes: New Insights from Phenomenological Modeling.
Cooperative binding is one of the most interesting and not fully understood phenomena involved in control and regulation of biological processes. Here we analyze the simplest phenomenological model that can account for cooperativity (i.e. ligand binding to a macromolecule with two binding sites) by...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4696654?pdf=render |
| _version_ | 1819290316062064640 |
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| author | Diego I Cattoni Osvaldo Chara Sergio B Kaufman F Luis González Flecha |
| author_facet | Diego I Cattoni Osvaldo Chara Sergio B Kaufman F Luis González Flecha |
| author_sort | Diego I Cattoni |
| collection | DOAJ |
| description | Cooperative binding is one of the most interesting and not fully understood phenomena involved in control and regulation of biological processes. Here we analyze the simplest phenomenological model that can account for cooperativity (i.e. ligand binding to a macromolecule with two binding sites) by generating equilibrium binding isotherms from deterministically simulated binding time courses. We show that the Hill coefficients determined for cooperative binding, provide a good measure of the Gibbs free energy of interaction among binding sites, and that their values are independent of the free energy of association for empty sites. We also conclude that although negative cooperativity and different classes of binding sites cannot be distinguished at equilibrium, they can be kinetically differentiated. This feature highlights the usefulness of pre-equilibrium time-resolved strategies to explore binding models as a key complement of equilibrium experiments. Furthermore, our analysis shows that under conditions of strong negative cooperativity, the existence of some binding sites can be overlooked, and experiments at very high ligand concentrations can be a valuable tool to unmask such sites. |
| first_indexed | 2024-12-24T03:20:48Z |
| format | Article |
| id | doaj.art-ec53b8d146af44c2aa34907a94d5d2f4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-24T03:20:48Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ec53b8d146af44c2aa34907a94d5d2f42022-12-21T17:17:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014604310.1371/journal.pone.0146043Cooperativity in Binding Processes: New Insights from Phenomenological Modeling.Diego I CattoniOsvaldo CharaSergio B KaufmanF Luis González FlechaCooperative binding is one of the most interesting and not fully understood phenomena involved in control and regulation of biological processes. Here we analyze the simplest phenomenological model that can account for cooperativity (i.e. ligand binding to a macromolecule with two binding sites) by generating equilibrium binding isotherms from deterministically simulated binding time courses. We show that the Hill coefficients determined for cooperative binding, provide a good measure of the Gibbs free energy of interaction among binding sites, and that their values are independent of the free energy of association for empty sites. We also conclude that although negative cooperativity and different classes of binding sites cannot be distinguished at equilibrium, they can be kinetically differentiated. This feature highlights the usefulness of pre-equilibrium time-resolved strategies to explore binding models as a key complement of equilibrium experiments. Furthermore, our analysis shows that under conditions of strong negative cooperativity, the existence of some binding sites can be overlooked, and experiments at very high ligand concentrations can be a valuable tool to unmask such sites.http://europepmc.org/articles/PMC4696654?pdf=render |
| spellingShingle | Diego I Cattoni Osvaldo Chara Sergio B Kaufman F Luis González Flecha Cooperativity in Binding Processes: New Insights from Phenomenological Modeling. PLoS ONE |
| title | Cooperativity in Binding Processes: New Insights from Phenomenological Modeling. |
| title_full | Cooperativity in Binding Processes: New Insights from Phenomenological Modeling. |
| title_fullStr | Cooperativity in Binding Processes: New Insights from Phenomenological Modeling. |
| title_full_unstemmed | Cooperativity in Binding Processes: New Insights from Phenomenological Modeling. |
| title_short | Cooperativity in Binding Processes: New Insights from Phenomenological Modeling. |
| title_sort | cooperativity in binding processes new insights from phenomenological modeling |
| url | http://europepmc.org/articles/PMC4696654?pdf=render |
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