Genomes to Life Contractor-Grantee Workshop III
February 6-9, 2005, Washington, D.C.
Technology Development and Use
Proteomics and Metabolomics
118
Dynameomics: Mass Annotation of Protein Dynamics through Molecular Dynamics Simulations of Fold-Space Representatives
David A. C. Beck* (dacb@u.washington.edu), Ryan Day, Kathryn A. Scott, R. Dustin Schaeffer, Robert E. Steward, Amanda L. Jonsson, Darwin O. V. Alonso, and Valerie Daggett
University of Washington, Seattle, WA
The Protein Data Bank (PDB) has been a tremendously useful repository of experimentally derived, static protein structures that have stimulated many important scientific discoveries. While the utility of static physical representations of proteins is not in doubt, as these molecules are fluid in vivo, there is a larger universe of knowledge to be tapped regarding the dynamics of proteins. Thus, we are constructing a complementary database comprised of molecular dynamics (MD) simulation [1] derived structures for representatives of all protein folds. We are calling this effort ‘dynameomics.’ For each fold (derived from consensus between SCOP, CATH, and DALI [2]) a representative protein is simulated in its native (i.e., biologically relevant) state and along its complete unfolding pathway by MD, the time-dependent integration of the classical equations of motion for molecular systems. There are approximately 1130 known non-redundant folds, of which we have simulated the first 30 that represent about 50% of known proteins. With the data resulting from our large database of MD simulations, we are data-mining for patterns and general features of transition, intermediate and denatured states to improve not only our understanding of protein dynamics but structure prediction, protein-protein and protein-ligand docking algorithms. Structure prediction remains one of the most elusive goals of protein chemistry. It is necessary to successfully predict native states of proteins, in order to translate the current deluge of genomic information into a form appropriate for functional identification of proteins from their primary sequence and rapid structure / dynamics based drug design. While these specific aims represent our immediate scientific goal for the dynameomics data, we are constructing a web site (http://www.dynameomics.org) for publication of the trajectories’ coordinate data as well as in-depth analyses so that others may avail themselves of the resource and initiate areas of inquiry that we cannot even begin to anticipate.
References
- Beck, D. A. C., and Daggett, V. (2004) Methods for Molecular Dynamics Simulations of Protein Folding / Unfolding in Solution, Methods 34, 112-120.
- Day, R., Beck, D. A. C., Armen, R. S., and Daggett, V. (2003) A consensus view of fold space: Combining SCOP, CATH, and the Dali Domain Dictionary, Protein Sci 12, 2150-2160.
* Presenting author
