@article {Kihara2002, title = {Ab initio protein structure prediction on a genomic scale: application to the Mycoplasma genitalium genome}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {99}, year = {2002}, month = {apr}, pages = {5993{\textendash}5998}, abstract = {An ab initio protein structure prediction procedure, TOUCHSTONE, was applied to all 85 small proteins of the Mycoplasma genitalium genome. TOUCHSTONE is based on a Monte Carlo refinement of a lattice model of proteins, which uses threading-based tertiary restraints. Such restraints are derived by extracting consensus contacts and local secondary structure from at least weakly scoring structures that, in some cases, can lack any global similarity to the sequence of interest. Selection of the native fold was done by using the convergence of the simulation from two different conformational search schemes and the lowest energy structure by a knowledge-based atomic-detailed potential. Among the 85 proteins, for 34 proteins with significant threading hits, the template structures were reasonably well reproduced. Of the remaining 51 proteins, 29 proteins converged to five or fewer clusters. In the test set, 84.8\% of the proteins that converged to five or fewer clusters had a correct fold among the clusters. If this statistic is simply applied, 24 proteins (84.8\% of the 29 proteins) may have correct folds. Thus, the topology of a total of 58 proteins probably has been correctly predicted. Based on these results, ab initio protein structure prediction is becoming a practical approach.}, keywords = {Algorithms, Bacterial, Databases as Topic, Genome, Models, Molecular, Monte Carlo Method, Mycoplasma, Mycoplasma: genetics, Protein Folding, Proteins, Proteins: chemistry, Software}, issn = {0027-8424}, doi = {10.1073/pnas.092135699}, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=122890\&tool=pmcentrez\&rendertype=abstract}, author = {Daisuke Kihara and Yang Zhang and Hui Lu and Andrzej Koli{\'n}ski and Jeffrey Skolnick} } @article {Kihara2001, title = {TOUCHSTONE: an ab initio protein structure prediction method that uses threading-based tertiary restraints}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {98}, number = {18}, year = {2001}, month = {aug}, pages = {10125{\textendash}30}, abstract = {The successful prediction of protein structure from amino acid sequence requires two features: an efficient conformational search algorithm and an energy function with a global minimum in the native state. As a step toward addressing both issues, a threading-based method of secondary and tertiary restraint prediction has been developed and applied to ab initio folding. Such restraints are derived by extracting consensus contacts and local secondary structure from at least weakly scoring structures that, in some cases, can lack any global similarity to the sequence of interest. Furthermore, to generate representative protein structures, a reduced lattice-based protein model is used with replica exchange Monte Carlo to explore conformational space. We report results on the application of this methodology, termed TOUCHSTONE, to 65 proteins whose lengths range from 39 to 146 residues. For 47 (40) proteins, a cluster centroid whose rms deviation from native is below 6.5 (5) A is found in one of the five lowest energy centroids. The number of correctly predicted proteins increases to 50 when atomic detail is added and a knowledge-based atomic potential is combined with clustered and nonclustered structures for candidate selection. The combination of the ratio of the relative number of contacts to the protein length and the number of clusters generated by the folding algorithm is a reliable indicator of the likelihood of successful fold prediction, thereby opening the way for genome-scale ab initio folding.}, keywords = {Algorithms, Computer Simulation, Models, Molecular, Monte Carlo Method, Protein Folding, Protein Structure, Proteins, Proteins: chemistry, Tertiary}, issn = {0027-8424}, doi = {10.1073/pnas.181328398}, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=56926\&tool=pmcentrez\&rendertype=abstract}, author = {Daisuke Kihara and Hui Lu and Andrzej Koli{\'n}ski and Jeffrey Skolnick} }