- SQL data analysis
- Property space analysis
- Denatured state structural analysis
- Native flexibility analysis
- Wavelet analysis
The data generated by Dynameomics (www.dynameomics.org) amounts to over 11,000 simulations of over 2,000 proteins. These data cannot be stored, organized, retrieved, and examined using traditional methods available in biology. In order to efficiently handle the dozens of terabytes of data that we have calculated, we have undergone a great number of bioinformatics initiatives. Traditional database techniques are not designed for data of the density and form such as ours, yet research will undoubtedly require simultaneous access to disparate pieces of our simulations. All of this requires a very firm and coherent structure and organization.
Additionally, traditional analysis techniques for simulations cannot be used for all research projects. Divining information from such a large database requires new high-throughput analysis techniques that can quickly pinpoint items of interest or similarity and that can rapidly summarize entire simulations. In order to achieve this end, we have been developing several new techniques. One of these techniques is the analysis of property space, which can be used to rapidly differentiate between native-state and denatured structures, enabling a high-throughput discovery of transition states. Another technique is flexibility analysis, which summarizes the primary modes of an entire simulation in a single structure. Conversely, wavelet analysis is a technique that examines find-detail oscillations of atoms and which has shown promise in pinpointing notable events in a simulation such as the rearrangement of a helix.
From all of these different atomic-level analyses, we can glean information to help us learn about protein folding pathways as well as behavioral differneces between wild type and disease-related mutant proteins. This understanding will lead to better design of drugs and interventions to inhibit the negative behaviors to rescue the mutant to its native function.
- Benson N. and Daggett V. Dynameomics: Large-Scale Assessment of Native Protein Flexibility. Protein Science 17: 2038-2050, 2009. [DOI]
- Law P.B. and Daggett V. The relationship between water bridges and the polyproline II conformation: a large-scale analysis of molecular dynamics simulations and crystal structures. Protein Engineering Design & Selection 23: 27-33, 2010. [DOI]
- Toofanny R.D., Jonsson A.L., and Daggett V. A Comprehensive Multidimensional-Embedded, One-Dimensional Reaction Coordinate for Protein Unfolding/Folding. Biophysical Journal 98:2671-2681, 2010. [DOI]
- Scouras A.D. and Daggett V. The dynameomics rotamer library: Amino acid side chain conformations and dynamics from comprehensive molecular dynamics simulations in water. Protein Science 20:341-352, 2010. [DOI]