title: Approaching Elastic Network Models to Molecular Dynamics Flexibility.
abstract: Elastic network models (ENMs) are coarse-grained descriptions of proteins as networks of coupled harmonic oscillators. However, despite their widespread application to study collective movements, there is still no consensus parametrization for the ENMs. When compared to molecular dynamics (MD) flexibility in solution, the ENMs tend to disperse the important motions into multiple modes. We present here a new ENM, trained against a database of atomistic MD trajectories. The role of residue connectivity, the analytical form of the force constants, and the threshold for interactions were systematically explored. We found that contacts between the three nearest sequence neighbors are crucial determinants of the fundamental motions. We developed a new general potential function including both the sequential and spatial relationships between interacting residue pairs which is robust against size and fold variations. The proposed model provides a systematic improvement compared to standard ENMs: Not only do its results match the MD results-even for long time scales-but also the model is able to capture large X-ray conformational transitions as well as NMR ensemble diversity.
authors.affiliation: Joint Research Program in Computational Biology from the Institute for Research in Biomedicine Barcelona (IRBB) and Barcelona Supercomputing Center (BSC), Barcelona, Spain, Chemical and Physical Biology, Centro de Investigaciones Biológicas, Madrid, Spain, Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain, and Skaggs School of Pharmacy, University of California-San Diego, La Jolla, California 92093.
authors.forename: Laura
authors.initials: L
authors.lastname: Orellana
authors.affiliation: Joint Research Program in Computational Biology from the Institute for Research in Biomedicine Barcelona (IRBB) and Barcelona Supercomputing Center (BSC), Barcelona, Spain, Chemical and Physical Biology, Centro de Investigaciones Biológicas, Madrid, Spain, Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain, and Skaggs School of Pharmacy, University of California-San Diego, La Jolla, California 92093.
authors.forename: Manuel
authors.initials: M
authors.lastname: Rueda
authors.affiliation: Joint Research Program in Computational Biology from the Institute for Research in Biomedicine Barcelona (IRBB) and Barcelona Supercomputing Center (BSC), Barcelona, Spain, Chemical and Physical Biology, Centro de Investigaciones Biológicas, Madrid, Spain, Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain, and Skaggs School of Pharmacy, University of California-San Diego, La Jolla, California 92093.
authors.forename: Carles
authors.initials: C
authors.lastname: Ferrer-Costa
authors.affiliation: Joint Research Program in Computational Biology from the Institute for Research in Biomedicine Barcelona (IRBB) and Barcelona Supercomputing Center (BSC), Barcelona, Spain, Chemical and Physical Biology, Centro de Investigaciones Biológicas, Madrid, Spain, Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain, and Skaggs School of Pharmacy, University of California-San Diego, La Jolla, California 92093.
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Lopez-Blanco
authors.affiliation: Joint Research Program in Computational Biology from the Institute for Research in Biomedicine Barcelona (IRBB) and Barcelona Supercomputing Center (BSC), Barcelona, Spain, Chemical and Physical Biology, Centro de Investigaciones Biológicas, Madrid, Spain, Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain, and Skaggs School of Pharmacy, University of California-San Diego, La Jolla, California 92093.
authors.forename: Pablo
authors.initials: P
authors.lastname: Chacón
authors.affiliation: Joint Research Program in Computational Biology from the Institute for Research in Biomedicine Barcelona (IRBB) and Barcelona Supercomputing Center (BSC), Barcelona, Spain, Chemical and Physical Biology, Centro de Investigaciones Biológicas, Madrid, Spain, Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain, and Skaggs School of Pharmacy, University of California-San Diego, La Jolla, California 92093.
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco