title: pK(a) Values of Titrable Amino Acids at the Water/Membrane Interface.
abstract: Peptides and proteins protonation equilibrium is strongly influenced by its surrounding media. Remarkably, until now, there have been no quantitative and systematic studies reporting the pK(a) shifts in the common titrable amino acids upon lipid membrane insertion. Here, we applied our recently developed CpHMD-L method to calculate the pK(a) values of titrable amino acid residues incorporated in Ala-based pentapeptides at the water/membrane interface. We observed that membrane insertion leads to desolvation and a clear stabilization of the neutral forms, and we quantified the increases/decreases of the pK(a) values in the anionic/cationic residues along the membrane normal. This work highlights the importance of properly modeling the protonation equilibrium in peptides and proteins interacting with membranes using molecular dynamics simulations.
authors: Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa , 1749-016 Lisboa, Portugal.
authors: Vitor H
authors: VH
authors: Teixeira
authors: Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa , 1749-016 Lisboa, Portugal.
authors: Diogo
authors: D
authors: Vila-Viçosa
authors: Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa , 1749-016 Lisboa, Portugal.
authors: Pedro B P S
authors: PB
authors: Reis
authors: Centro de Química e Bioquímica, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa , 1749-016 Lisboa, Portugal.
authors: Miguel
authors: M
authors: Machuqueiro
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D014867:Water / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D008051:Lipid Bilayers; D014867:Water