dTASSER is the implementation of the PROSPECTOR/TASSER methodology for protein structure prediction from J. Skolnick into the Berkeley Open Infrastructure for Network Computing (BOINC) hosted at PREDICTOR@HOME in C. L. Brooks, III lab.
Despite considerable efforts in recent years, predicting the native structure of a protein from its amino acid sequence is still one of the most important and challenging problems in structural biology. Based on recent studies, it appears that a combination of theoretical methods and new computational technologies are necessary to further advance this area of research. PREDICTOR@HOME is a world-community experiment and effort to use distributed world-wide-web volunteer resources to assemble a supercomputer aimed at testing and evaluating new algorithms for protein structure prediction. Additionally, new structure prediction algorithms have emerged in the last few years: one of the most recent is TASSER (Threading / ASSembly / Refinement).
In the first stage of the project the resources and computing power of a distributed system such as PREDICTOR@HOME are initially used to critically test TASSER on a number of biological systems, including both soluble and transmembrane proteins. Once validated, our goal in the near future is to use these tools in other projects such as the structural prediction of viral capsids or aiding to the efforts in trying to cure diseases like tuberculosis.
J. Skolnick's methodology is a hierarchical approach that consists of template identification (PROSPECTOR), followed by tertiary structure assembly by rearranging continuous template fragments (TASSER). Assembly occurs using replica exchange hyperbolic Monte Carlo (RXHMC) sampling under the guide of an optimized, reduced force field that includes knowledge-based statistical potentials and spatial restraints extracted from threading alignments. Models are selected from the RXHMC trajectories in the low-temperature replicas using a clustering algorithm (sPICKER).
[PROTEINS 56:502 (2004)]
PROtein Structure Predictor Employing Combined Threading to Optimize Results: Third generation of threading algorithms.
For a given Target:
[PNAS 101:7594 (2004)]
Threading ASSEmbly Refinement: Direct descendant of TOUCHSTONE; ab initio protein structure prediction. [PNAS 98:10125 (2001), Biophys. J. 85:1145 (2003)]
CAS force field: Cα Atoms and Side chain centers of mass (SG) are used to represent the protein. This force field uses the following information:
So, for a given threading Template:
[J. Comput. Chem. 25:865 (2004)]
Structure PICKER: Direct descendant of SCAR [J. Comp. Chem. 22:339 (2001)]
Identifies near-native folds by clustering structures:
Several results suggest that it can be done if:
TASSER extended sampling takes more than 2 weeks on a single processor for a 400 residue protein!