Development of a Structure-Based, pH-Dependent Lipophilicity Scale of Amino Acids from Continuum Solvation Calculations
Lipophilicity is a fundamental property to characterize the structure and function of proteins, motivating the development of lipophilicity scales. Here we report a versatile strategy to derive a pH-adapted scale that relies on theoretical estimates of distribution coefficients from conformational e...
| Autores: | , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/168798 |
| Acceso en línea: | https://hdl.handle.net/2445/168798 |
| Access Level: | acceso abierto |
| Palabra clave: | Bioquímica Farmacologia Biochemistry Pharmacology |
| Sumario: | Lipophilicity is a fundamental property to characterize the structure and function of proteins, motivating the development of lipophilicity scales. Here we report a versatile strategy to derive a pH-adapted scale that relies on theoretical estimates of distribution coefficients from conformational ensembles of amino acids. This is accomplished by using an accurately parametrized version of the IEFPCM/MST continuum solvation model, as an effective way to describe the partitioning between n-octanol and water, in conjunction with a formalism that combines partition coefficients of neutral and ionic species of residues, and the corresponding pKa of ionizable groups. Two weighting schemes are considered to derive solvent-like and protein-like scales, which have been calibrated by comparison with other experimental scales developed in different chemical/biological environments and pH conditions, as well as by examining properties such as the retention time of small peptides and the recognition of antigenic peptides. A straightforward extension to nonstandard residues is enabled by this efficient methodological strategy. |
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