@article {Ortiz1998a, title = {Nativelike topology assembly of small proteins using predicted restraints in Monte Carlo folding simulations}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {95}, number = {3}, year = {1998}, month = {feb}, pages = {1020{\textendash}1025}, abstract = {By incorporating predicted secondary and tertiary restraints derived from multiple sequence alignments into ab initio folding simulations, it has been possible to assemble native-like tertiary structures for a test set of 19 nonhomologous proteins ranging from 29 to 100 residues in length and representing all secondary structural classes. Secondary structural restraints are provided by the PHD secondary structure prediction algorithm that incorporates multiple sequence information. Multiple sequence alignments also provide predicted tertiary restraints via a two-step process: First, seed side chain contacts are selected from a correlated mutation analysis, and then an inverse folding algorithm expands these seed contacts. The predicted secondary and tertiary restraints are incorporated into a lattice-based, reduced protein model for structure assembly and refinement. The resulting native-like topologies exhibit a coordinate root-mean-square deviation from native for the whole chain between 3.1 and 6.7 A, with values ranging from 2.6 to 4.1 A over approximately 80\% of the structure. Overall, this study suggests that the use of restraints derived from multiple sequence alignments combined with a fold assembly algorithm is a promising approach to the prediction of the global topology of small proteins.}, keywords = {Algorithms, Models, Molecular, Monte Carlo Method, Protein Folding, Protein Structure, Secondary, Sequence Alignment, Software, Tertiary}, issn = {0027-8424}, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=18658\&tool=pmcentrez\&rendertype=abstract}, author = {Angel. R. Ortiz and Andrzej Koli{\'n}ski and Jeffrey Skolnick} } @article {Ortiz1998b, title = {Tertiary structure prediction of the KIX domain of CBP using Monte Carlo simulations driven by restraints derived from multiple sequence alignments}, journal = {Proteins}, volume = {30}, number = {3}, year = {1998}, pages = {287{\textendash}294}, abstract = {Using a recently developed protein folding algorithm, a prediction of the tertiary structure of the KIX domain of the CREB binding protein is described. The method incorporates predicted secondary and tertiary restraints derived from multiple sequence alignments in a reduced protein model whose conformational space is explored by Monte Carlo dynamics. Secondary structure restraints are provided by the PHD secondary structure prediction algorithm that was modified for the presence of predicted U-turns, i.e., regions where the chain reverses global direction. Tertiary restraints are obtained via a two-step process: First, seed side-chain contacts are identified from a correlated mutation analysis, and then, a threading-based algorithm expands the number of these seed contacts. Blind predictions indicate that the KIX domain is a putative three-helix bundle, although the chirality of the bundle could not be uniquely determined. The expected root-mean-square deviation for the correct chirality of the KIX domain is between 5.0 and 6.2 A. This is to be compared with the estimate of 12.9 A that would be expected by a random prediction, using the model of F. Cohen and M. Sternberg (J. Mol. Biol. 138:321-333, 1980).}, keywords = {Algorithms, Amino Acid Sequence, CREB-Binding Protein, Databases as Topic, Models, Molecular, Molecular Sequence Data, Monte Carlo Method, Mutation, Mutation: genetics, Nuclear Proteins, Nuclear Proteins: chemistry, Protein Folding, Protein Structure, Secondary, Sequence Alignment, Tertiary, Trans-Activators, Transcription Factors, Transcription Factors: chemistry}, issn = {0887-3585}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9517544}, author = {Angel. R. Ortiz and Andrzej Koli{\'n}ski and Jeffrey Skolnick} }