title: Core deformations in protein families: a physical perspective.
abstract: An analysis is presented on how structural cores change shape within protein families, and whether or not there is a relationship between these structural changes and the vibrational modes that proteins experiment due to topological constraints. A set of 13 representative and well-populated protein families are studied. The evolutionary directions of deformation are obtained by applying a new multiple structural alignment technique to superimpose the structures and extract a conserved core, together with Principal Components Analysis (PCA) to extract the main deformation modes. A low-resolution Normal Mode Analysis (NMA) technique is used in parallel to study the properties of the mechanical core plasticity of the same proteins. We find that the evolutionary deformations span a low dimensional space. A statistically significant correspondence exists between these principal deformations and the vibrational modes accessible to a particular topology. We conclude that, to a significant extent, the structures of evolving proteins seem to respond to sequence changes by collective deformations along combinations of low-frequency modes. The findings have implications in structure prediction by homology modeling.
authors.affiliation: Bioinformatics Unit, Centro de Biologia Molecular Severo Ochoa, CSIC-UAM, Universidad Autonoma de Madrid, Cantoblanco 28049, 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: D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D025341:Principal Component Analysis; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000145:classification* / Q000378:metabolism; D014732:Vibration
chemical_list: D011506:Proteins