Integration with SQL Server
Parallelization of MD Code
Realistic simulation of biological macromolecules in solution necessitates rigorous molecular dynamics (MD) methods. As such, improving the fidelity of our MD calculations is of great interest to our lab, as is including other biologically or experimentally relevant cosolvents, ligands, etc. To these ends, we actively develop new force-field parameters for necessary molecules that in simulation reproduce experimental qualities of the target molecules.
When the simulations are complete, we run a large suite of analyses for interpreting the trajectory and for comparison to experimental observables from NMR experiments, CD, etc. As new techniques are developed, in NMR for example, we have developed new analyses to use to evaluate our simulations against experiment.
To these ends, we have developed in lucem Molecular Mechanics (ilmm), a scalable parallel molecular mechanics engine. It is used for simulation proteins in explicit solvents, such as water, urea, gndHCl, TMAO, etc. or mixtures of these, as well as membranes or anchored to membranes (via GPI). Our extensive analysis package includes structure comparison (RMSD, CONGENEAL), dihedral reporting and φ/ψ statistics, solvent accessible surface area (SASA), identification of intra and intermolecular contacts, NMR NOE, order parameters (S2), residual dipolar coupling (RDC), diffusion, radial distribution function, and solvent density function. In addition to standard molecular dynamics, the package can perform: minimization, simulated annealing, replica-exchange molecular dynamics, and distance geometry.
We have also created an XML Schema for describing general molecular mechanics parameter libraries which we now use with our simulation engine. See a graphical representation and read more about it here.
From these simulations comes a vast amount of complex data, which we organize in a Microsoft SQL data warehouse (www.dynameomics.org). We are also developing novel approaches to dynamic, interactive data visualization through the use of the graphical user interfaces, real-time video game quality rendering engines, and hardware accelerated data analysis.
- Beck D.A.C., McCully M.E., Alonso D.O.V., and Daggett V. (2000-2012) in lucem Molecular Mechanics (ilmm), University of Washington, Seattle.
- Beck D.A.C. and Daggett V. Methods for Molecular Dynamics Simulations of Protein Folding/Unfolding in Solution, Methods 34: 112-120, 2004. [DOI]
- Beck D.A.C., Armen R.S., and Daggett V. Cutoff size need not strongly influence molecular dynamics results on solvated polypeptides. Biochemistry 44: 609-616, 2005. [DOI]
- Bromley D., Rysavy S., Beck D.A.C., and Daggett V. DIVE: A Data Intensive Visualization Engine. Microsoft Research eScience Workshop, 2010 (speaker). [HTML]