Open Access Highly Accessed Research article

Comparison of molecular dynamics and superfamily spaces of protein domain deformation

Javier A Velázquez-Muriel13, Manuel Rueda249, Isabel Cuesta1, Alberto Pascual-Montano5, Modesto Orozco2679* and José-María Carazo18*

Author Affiliations

1 Centro Nacional de Biotecnología-CSIC, Campus Universidad Autónoma, 28049 Madrid, Spain

2 Molecular Modeling and Bioinformatics Unit, IRB-BSC Joint Research Program in Computational Biology, Institute for Research in Biomedicine, Josep Samitier 1-5, Barcelona 08028, Spain

3 University of California, San Francisco, Department of Biopharmaceutical Sciences and Pharmaceutical Chemistry, 1700 4th St. UCSF/MC 2552, Byers Hall Room 503, San Francisco, CA 94158-2330, USA

4 The Scripps Research Institute, Department of Molecular Biology, 10550 North Torrey Pines Road, Mail TPC-28, La Jolla, California, 92037, USA

5 Departament Arquitectura de Computadores y Automática, Facultad de Ciencias Físicas, Universidad Complutense, 28040 Madrid, Spain

6 Departament de Bioquímica i Biología Molecular, Facultat de Biología, Universitat de Barcelona, Avgda Diagonal 645, Barcelona 08028, Spain

7 National Institute of Bioinformatics, Parc Científic de Barcelona, Josep Samitier 1-5, Barcelona 08028, Spain

8 National Institute of Bioinformatics, Centro Nacional de Biotecnología, CSIC, Madrid, Spain

9 Barcelona Supercomputing Center, Jordi Girona 29, Barcelona 08034, Spain

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BMC Structural Biology 2009, 9:6  doi:10.1186/1472-6807-9-6

Published: 17 February 2009



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).


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.


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.