title: An analysis of core deformations in protein superfamilies.
abstract: An analysis is presented on how structural cores modify their shape across homologous proteins, and whether or not a relationship exists between these structural changes and the vibrational normal modes that proteins experience as a result of the topological constraints imposed by the fold. A set of 35 representative, well-populated protein families is studied. The evolutionary directions of deformation are obtained by using multiple structural alignments to superimpose the structures and extract a conserved core, together with principal components analysis to extract the main deformation modes from the three-dimensional superimposition. In parallel, a low-resolution normal mode analysis technique is employed to study the properties of the mechanical core plasticity of these same families. We show that the evolutionary deformations span a low dimensional space of 4-5 dimensions on average. A statistically significant correspondence exists between these principal deformations and the approximately 20 slowest vibrational modes accessible to a particular topology. We conclude that, to a significant extent, the structural response of a protein topology to sequence changes takes place by means of collective deformations along combinations of a small number of low-frequency modes. The findings have implications in structure prediction by homology modeling.
authors.affiliation: Bioinformatics Unit, Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Cantoblanco, Madrid, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Leo-Macias
authors.forename: Pedro
authors.initials: P
authors.lastname: Lopez-Romero
authors.forename: Dmitry
authors.initials: D
authors.lastname: Lupyan
authors.forename: Daniel
authors.initials: D
authors.lastname: Zerbino
authors.forename: Angel R
authors.initials: AR
authors.lastname: Ortiz
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D017124:Conserved Sequence; D030562:Databases, Protein; D019143:Evolution, Molecular; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D025341:Principal Component Analysis; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000145:classification*; D016415:Sequence Alignment / Q000379:methods*; D017386:Sequence Homology, Amino Acid
chemical_list: D011506:Proteins