title: Sequence co-evolutionary information is a natural partner to minimally-frustrated models of biomolecular dynamics.
abstract: Experimentally derived structural constraints have been crucial to the implementation of computational models of biomolecular dynamics. For example, not only does crystallography provide essential starting points for molecular simulations but also high-resolution structures permit for parameterization of simplified models. Since the energy landscapes for proteins and other biomolecules have been shown to be minimally frustrated and therefore funneled, these structure-based models have played a major role in understanding the mechanisms governing folding and many functions of these systems. Structural information, however, may be limited in many interesting cases. Recently, the statistical analysis of residue co-evolution in families of protein sequences has provided a complementary method of discovering residue-residue contact interactions involved in functional configurations. These functional configurations are often transient and difficult to capture experimentally. Thus, co-evolutionary information can be merged with that available for experimentally characterized low free-energy structures, in order to more fully capture the true underlying biomolecular energy landscape.
authors.affiliation: Center for Theoretical Biological Physics, Rice University, Houston, TX, USA; Kristallographie, Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Noel
authors.affiliation: Department of Biological Sciences, University of Texas at Dallas, Richardson, TX, USA.
authors.forename: Faruck
authors.initials: F
authors.lastname: Morcos
authors.affiliation: Center for Theoretical Biological Physics, Rice University, Houston, TX, USA.
authors.forename: Jose N
authors.initials: JN
authors.lastname: Onuchic
keywords: Direct coupling analysis; biomolecular dynamics; frustrated protein models; minimally frustrated models; nuclear magnetic resonance; protein structure model; x-ray crystallography