title: Comparison of molecular dynamics and superfamily spaces of protein domain deformation.
abstract: BACKGROUND
  It is well known the strong relationship between protein structure and flexibility, on one hand, and biological protein function, on the other hand. Technically, protein flexibility exploration is an essential task in many applications, such as protein structure prediction and modeling. In this contribution we have compared two different approaches to explore the flexibility space of protein domains: i) molecular dynamics (MD-space), and ii) the study of the structural changes within superfamily (SF-space).
  
  
  RESULTS
  Our analysis indicates that the MD-space and the SF-space display a significant overlap, but are still different enough to be considered as complementary. The SF-space space is wider but less complex than the MD-space, irrespective of the number of members in the superfamily. Also, the SF-space does not sample all possibilities offered by the MD-space, but often introduces very large changes along just a few deformation modes, whose number tend to a plateau as the number of related folds in the superfamily increases.
  
  
  CONCLUSIONS
  Theoretically, we obtained two conclusions. First, that function restricts the access to some flexibility patterns to evolution, as we observe that when a superfamily member changes to become another, the path does not completely overlap with the physical deformability. Second, that conformational changes from variation in a superfamily are larger and much simpler than those allowed by physical deformability. Methodologically, the conclusion is that both spaces studied are complementary, and have different size and complexity. We expect this fact to have application in fields as 3D-EM/X-ray hybrid models or ab initio protein folding.
authors.affiliation: Centro Nacional de Biotecnología-CSIC, Campus Universidad Autónoma, 28049 Madrid, Spain. javi.velazquez@gmail.com
authors.forename: Javier A
authors.initials: JA
authors.lastname: Velázquez-Muriel
authors.forename: Manuel
authors.initials: M
authors.lastname: Rueda
authors.forename: Isabel
authors.initials: I
authors.lastname: Cuesta
authors.forename: Alberto
authors.initials: A
authors.lastname: Pascual-Montano
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco
authors.forename: José-María
authors.initials: JM
authors.lastname: Carazo
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid
chemical_list: D011506:Proteins