title: Analysis of the interactions of sulfur-containing amino acids in membrane proteins.
abstract: The interactions of Met and Cys with other amino acid side chains have received little attention, in contrast to aromatic-aromatic, aromatic-aliphatic or/and aliphatic-aliphatic interactions. Precisely, these are the only amino acids that contain a sulfur atom, which is highly polarizable and, thus, likely to participate in strong Van der Waals interactions. Analysis of the interactions present in membrane protein crystal structures, together with the characterization of their strength in small-molecule model systems at the ab-initio level, predicts that Met-Met interactions are stronger than Met-Cys ≈ Met-Phe ≈ Cys-Phe interactions, stronger than Phe-Phe ≈ Phe-Leu interactions, stronger than the Met-Leu interaction, and stronger than Leu-Leu ≈ Cys-Leu interactions. These results show that sulfur-containing amino acids form stronger interactions than aromatic or aliphatic amino acids. Thus, these amino acids may provide additional driving forces for maintaining the 3D structure of membrane proteins and may provide functional specificity.
authors.affiliation: Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, E-08193, Bellaterra, Spain.
authors.forename: José C
authors.initials: JC
authors.lastname: Gómez-Tamayo
authors.affiliation: Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, E-08193, Bellaterra, Spain.
authors.forename: Arnau
authors.initials: A
authors.lastname: Cordomí
authors.affiliation: Departament de Biologia de Sistemes, Universitat de Vic, Vic, 08500, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Olivella
authors.affiliation: Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, E-08193, Bellaterra, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mayol
authors.affiliation: Laboratoire de Physique et Chimie des Nano-Objets University of Toulouse, CNRS, INSA, INSERM, Toulouse, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fourmy
authors.affiliation: Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, E-08193, Bellaterra, Spain.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pardo
mesh_terms: D000818:Animals; D001419:Bacteria / Q000737:chemistry; D001665:Binding Sites; D019295:Computational Biology; D018360:Crystallography, X-Ray; D057225:Data Mining; D030562:Databases, Protein; D004151:Dipeptides / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013455:Sulfur / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D004151:Dipeptides; D008565:Membrane Proteins; C075870:methionylphenylalanine; C026650:phenylalanylphenylalanine; C038361:leucylleucine; C033517:phenylalanylleucine; C034758:methionylmethionine; D013455:Sulfur
keywords: membrane proteins; mining of crystal structures; sulfur-containing amino acids; van der Waals interactions