Coupling between conformation and proton binding in proteins

• Autores: Vila, Jorge Alberto; Ripoll, Daniel R.; Arnautova, Yelena A.; Vorobjev, Yury N.; Scheraga, Harold A.
• Año de publicación: 2005
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: CHARGE DISTRIBUTION; ELECTROSTATICS; SOLVATION; PROTEIN CONFORMATION; PROTON BINDING
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Interest centers here on whether the use of a fixed charge distribution of a protein solute, or a treatment that considers proton-binding equilibria by solving the Poisson equation, is a better approach to discriminate native from non-native conformations of proteins. In this analysis of the charge distribution of 7 proteins, we estimate the solvation free energy contribution to the total free energy by exploring the 2ζ possible ionization states of the whole molecule, with ζ being the number of ionizable groups in the amino acid sequence, for every conformation in the ensembles of 7 proteins. As an additional consideration of the role of electrostatic interactions in determining the charge distribution of native folds, we carried out a comparison of alternative charge assignment models for the ionizable residues in a set of 21 native-like proteins. The results of this work indicate that (1) for 6 out of 7 proteins, estimation of solvent polarization based on the Generalized Born model with a fixed charge distribution provides the optimal trade-off between accuracy, with respect to the Poisson equation, and speed when compared to the accessible surface area model; for the seventh protein, consideration of all possible ionization states of the whole molecule appears to be crucial to discriminate the native from non-native conformations; (2) significant differences in the degree of ionization and hence the charge distribution for native folds are found between the different charge models examined; (3) the stability of the native state is determined by a delicate balance of all the energy components, and (4) conformational entropy, and hence the dynamics of folding, may play a crucial role for a successful ab initio protein folding prediction.
Fil: Vila, Jorge Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; Argentina. Cornell University; Estados Unidos
Fil: Ripoll, Daniel R.. Cornell University; Estados Unidos
Fil: Arnautova, Yelena A.. Cornell University; Estados Unidos
Fil: Vorobjev, Yury N.. Institute of Chemical Biology and Fundamental Medicine of Siberian Brunch of Russian Academy of Science; Rusia
Fil: Scheraga, Harold A.. Cornell University; Estados Unidos