%0 Journal Article %J Journal of Molecular Biology %D 1998 %T Fold assembly of small proteins using monte carlo simulations driven by restraints derived from multiple sequence alignments %A Angel. R. Ortiz %A Andrzej Koliński %A Jeffrey Skolnick %K Amino Acid Sequence %K Chemical %K Models %K Molecular Sequence Data %K Monte Carlo Method %K Protein Folding %K Protein Structure %K Secondary %K Tertiary %X 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. %B Journal of Molecular Biology %V 277 %P 419–448 %8 mar %G eng %U http://www.ncbi.nlm.nih.gov/pubmed/9514747 %R 10.1006/jmbi.1997.1595 %0 Journal Article %J Proteins %D 1996 %T Folding simulations and computer redesign of protein A three-helix bundle motifs %A Krzysztof A. Olszewski %A Andrzej Koliński %A Jeffrey Skolnick %K Computer Simulation %K Monte Carlo Method %K Mutation %K Protein Conformation %K Protein Folding %K Staphylococcal Protein A %K Staphylococcal Protein A: chemistry %X In solution, the B domain of protein A from Staphylococcus aureus (B domain) possesses a three-helix bundle structure. This simple motif has been previously reproduced by Kolinski and Skolnick (Proteins 18: 353-366, 1994) using a reduced representation lattice model of proteins with a statistical interaction scheme. In this paper, an improved version of the potential has been used, and the robustness of this result has been tested by folding from the random state a set of three-helix bundle proteins that are highly homologous to the B domain of protein A. Furthermore, an attempt to redesign the B domain native structure to its topological mirror image fold has been made by multiple mutations of the hydrophobic core and the turn region between helices I and II. A sieve method for scanning a large set of mutations to search for this desired property has been proposed. It has been shown that mutations of native B domain hydrophobic core do not introduce significant changes in the protein motif. Mutations in the turn region were also very conservative; nevertheless, a few mutants acquired the desired topological mirror image motif. A set of all atom models of the most probable mutant was reconstructed from the reduced models and refined using a molecular dynamics algorithm in the presence of water. The packing of all atom structures obtained corroborates the lattice model results. We conclude that the change in the handedness of the turn induced by the mutations, augmented by the repacking of hydrophobic core and the additional burial of the second helix N-cap side chain, are responsible for the predicted preferential adoption of the mirror image structure. %B Proteins %V 25 %P 286–299 %8 jul %G eng %U http://www.ncbi.nlm.nih.gov/pubmed/8844865 %R 10.1002/(SICI)1097-0134(199607)25:3<286::AID-PROT2>3.0.CO;2-E %0 Journal Article %J Proceedings of the National Academy of Sciences of the United States of America %D 1993 %T From independent modules to molten globules: observations on the nature of protein folding intermediates %A Jeffrey Skolnick %A Andrzej Koliński %A Adam Godzik %K Binding Sites %K Isomerases %K Isomerases: chemistry %K Protein Disulfide-Isomerases %K Protein Folding %K Protein Structure %K Proteins %K Proteins: chemistry %K Secondary %B Proceedings of the National Academy of Sciences of the United States of America %V 90 %P 2099–100 %G eng %U http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=46030&tool=pmcentrez&rendertype=abstract