@article {Ortiz1998, title = {Fold assembly of small proteins using monte carlo simulations driven by restraints derived from multiple sequence alignments}, journal = {Journal of Molecular Biology}, volume = {277}, number = {2}, year = {1998}, month = {mar}, pages = {419{\textendash}448}, abstract = {The feasibility of predicting the global fold of small proteins by incorporating predicted secondary and tertiary restraints into ab initio folding simulations has been demonstrated on a test set comprised of 20 non-homologous proteins, of which one was a blind prediction of target 42 in the recent CASP2 contest. These proteins contain from 37 to 100 residues and represent all secondary structural classes and a representative variety of global topologies. Secondary structure restraints are provided by the PHD secondary structure prediction algorithm that incorporates multiple sequence information. Predicted tertiary restraints are derived from multiple sequence alignments via a two-step process. First, seed side-chain contacts are identified from correlated mutation analysis, and then a threading-based algorithm is used to expand the number of these seed contacts. A lattice-based reduced protein model and a folding algorithm designed to incorporate these predicted restraints is described. Depending upon fold complexity, it is possible to assemble native-like topologies whose coordinate root-mean-square deviation from native is between 3.0 A and 6.5 A. The requisite level of accuracy in side-chain contact map prediction can be roughly 25\% on average, provided that about 60\% of the contact predictions are correct within +/-1 residue and 95\% of the predictions are correct within +/-4 residues. Precision in tertiary contact prediction is more critical than absolute accuracy. Furthermore, only a subset of the tertiary contacts, on the order of 25\% of the total, is sufficient for successful topology assembly. Overall, this study suggests that the use of restraints derived from multiple sequence alignments combined with a fold assembly algorithm holds considerable promise for the prediction of the global topology of small proteins.}, keywords = {Amino Acid Sequence, Chemical, Models, Molecular Sequence Data, Monte Carlo Method, Protein Folding, Protein Structure, Secondary, Tertiary}, issn = {0022-2836}, doi = {10.1006/jmbi.1997.1595}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9514747}, author = {Angel. R. Ortiz and Andrzej Koli{\'n}ski and Jeffrey Skolnick} } @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} } @article {Skolnick1997, title = {MONSSTER: a method for folding globular proteins with a small number of distance restraints}, journal = {Journal of Molecular Biology}, volume = {265}, number = {2}, year = {1997}, month = {jan}, pages = {217{\textendash}241}, abstract = {The MONSSTER (MOdeling of New Structures from Secondary and TEritary Restraints) method for folding of proteins using a small number of long-distance restraints (which can be up to seven times less than the total number of residues) and some knowledge of the secondary structure of regular fragments is described. The method employs a high-coordination lattice representation of the protein chain that incorporates a variety of potentials designed to produce protein-like behaviour. These include statistical preferences for secondary structure, side-chain burial interactions, and a hydrogen-bond potential. Using this algorithm, several globular proteins (1ctf, 2gbl, 2trx, 3fxn, 1mba, 1pcy and 6pti) have been folded to moderate-resolution, native-like compact states. For example, the 68 residue 1ctf molecule having ten loosely defined, long-range restraints was reproducibly obtained with a C alpha-backbone root-mean-square deviation (RMSD) from native of about 4. A. Flavodoxin with 35 restraints has been folded to structures whose average RMSD is 4.28 A. Furthermore, using just 20 restraints, myoglobin, which is a 146 residue helical protein, has been folded to structures whose average RMSD from native is 5.65 A. Plastocyanin with 25 long-range restraints adopts conformations whose average RMSD is 5.44 A. Possible applications of the proposed approach to the refinement of structures from NMR data, homology model-building and the determination of tertiary structure when the secondary structure and a small number of restraints are predicted are briefly discussed.}, keywords = {Algorithms, Aprotinin, Aprotinin: chemistry, Bacterial Proteins, Bacterial Proteins: chemistry, Computer Graphics, Computer Simulation, Flavodoxin, Flavodoxin: chemistry, Models, Molecular, Myoglobin, Myoglobin: chemistry, Plastocyanin, Plastocyanin: chemistry, Protein Conformation, Protein Folding, Protein Structure, Secondary, Tertiary, Thioredoxins, Thioredoxins: chemistry}, issn = {0022-2836}, doi = {10.1006/jmbi.1996.0720}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9020984}, author = {Jeffrey Skolnick and Andrzej Koli{\'n}ski and Angel. R. Ortiz} }