@article {Boniecki2003, title = {Protein fragment reconstruction using various modeling techniques}, journal = {Journal of Computer-Aided Molecular Design}, volume = {17}, number = {11}, year = {2003}, month = {nov}, pages = {725{\textendash}38}, abstract = {Recently developed reduced models of proteins with knowledge-based force fields have been applied to a specific case of comparative modeling. From twenty high resolution protein structures of various structural classes, significant fragments of their chains have been removed and treated as unknown. The remaining portions of the structures were treated as fixed - i.e., as templates with an exact alignment. Then, the missed fragments were reconstructed using several modeling tools. These included three reduced types of protein models: the lattice SICHO (Side Chain Only) model, the lattice CABS (Calpha + Cbeta + Side group) model and an off-lattice model similar to the CABS model and called REFINER. The obtained reduced models were compared with more standard comparative modeling tools such as MODELLER and the SWISS-MODEL server. The reduced model results are qualitatively better for the higher resolution lattice models, clearly suggesting that these are now mature, competitive and complementary (in the range of sparse alignments) to the classical tools of comparative modeling. Comparison between the various reduced models strongly suggests that the essential ingredient for the sucessful and accurate modeling of protein structures is not the representation of conformational space (lattice, off-lattice, all-atom) but, rather, the specificity of the force fields used and, perhaps, the sampling techniques employed. These conclusions are encouraging for the future application of the fast reduced models in comparative modeling on a genomic scale.}, keywords = {Amino Acid Sequence, Binding Sites, Hydrogen Bonding, Models, Molecular, Peptide Fragments, Peptide Fragments: chemistry, Protein Conformation, Protein Structure, Proteins, Proteins: chemistry, Secondary}, issn = {0920-654X}, url = {http://www.ncbi.nlm.nih.gov/pubmed/15072433}, author = {Michal Boniecki and Piotr Rotkiewicz and Jeffrey Skolnick and Andrzej Koli{\'n}ski} } @article {Kolinski2001, title = {Generalized comparative modeling (GENECOMP): a combination of sequence comparison, threading, and lattice modeling for protein structure prediction and refinement}, journal = {Proteins}, volume = {44}, number = {2}, year = {2001}, month = {aug}, pages = {133{\textendash}149}, abstract = {An improved generalized comparative modeling method, GENECOMP, for the refinement of threading models is developed and validated on the Fischer database of 68 probe-template pairs, a standard benchmark used to evaluate threading approaches. The basic idea is to perform ab initio folding using a lattice protein model, SICHO, near the template provided by the new threading algorithm PROSPECTOR. PROSPECTOR also provides predicted contacts and secondary structure for the template-aligned regions, and possibly for the unaligned regions by garnering additional information from other top-scoring threaded structures. Since the lowest-energy structure generated by the simulations is not necessarily the best structure, we employed two structure-selection protocols: distance geometry and clustering. In general, clustering is found to generate somewhat better quality structures in 38 of 68 cases. When applied to the Fischer database, the protocol does no harm and in a significant number of cases improves upon the initial threading model, sometimes dramatically. The procedure is readily automated and can be implemented on a genomic scale.}, keywords = {Algorithms, Chemical, Combinatorial Chemistry Techniques, Combinatorial Chemistry Techniques: methods, Computational Biology, Computational Biology: methods, Computer Simulation, Databases, Factual, Models, Molecular, Monte Carlo Method, Protein Folding, Proteins, Proteins: chemistry, Sequence Alignment, Sequence Alignment: methods}, issn = {0887-3585}, url = {http://www.ncbi.nlm.nih.gov/pubmed/11391776}, author = {Andrzej Koli{\'n}ski and Marcos Betancourt and Daisuke Kihara and Piotr Rotkiewicz and Jeffrey Skolnick} } @article {Feig2000, title = {Accurate reconstruction of all-atom protein representations from side-chain-based low-resolution models}, journal = {Proteins}, volume = {41}, number = {1}, year = {2000}, month = {oct}, pages = {86{\textendash}97}, abstract = {A procedure for the reconstruction of all-atom protein structures from side-chain center-based low-resolution models is introduced and applied to a set of test proteins with high-resolution X-ray structures. The accuracy of the rebuilt all-atom models is measured by root mean square deviations to the corresponding X-ray structures and percentages of correct chi(1) and chi(2) side-chain dihedrals. The benefit of including C(alpha) positions in the low-resolution model is examined, and the effect of lattice-based models on the reconstruction accuracy is discussed. Programs and scripts implementing the reconstruction procedure are made available through the NIH research resource for Multiscale Modeling Tools in Structural Biology (http://mmtsb.scripps.edu).}, keywords = {Models, Molecular, Proteins, Proteins: chemistry}, issn = {0887-3585}, url = {http://www.ncbi.nlm.nih.gov/pubmed/10944396}, author = {M. Feig and Piotr Rotkiewicz and Andrzej Koli{\'n}ski and Jeffrey Skolnick and Charles L. Brooks III} } @article {Ortiz1999, title = {Ab initio folding of proteins using restraints derived from evolutionary information}, journal = {Proteins}, volume = {Suppl. 3}, number = {May}, year = {1999}, month = {jan}, pages = {177{\textendash}185}, abstract = {We present our predictions in the ab initio structure prediction category of CASP3. Eleven targets were folded, using a method based on a Monte Carlo search driven by secondary and tertiary restraints derived from multiple sequence alignments. Our results can be qualitatively summarized as follows: The global fold can be considered "correct" for targets 65 and 74, "almost correct" for targets 64, 75, and 77, "half-correct" for target 79, and "wrong" for targets 52, 56, 59, and 63. Target 72 has not yet been solved experimentally. On average, for small helical and alpha/beta proteins (on the order of 110 residues or smaller), the method predicted low resolution structures with a reasonably good prediction of the global topology. Most encouraging is that in some situations, such as with target 75 and, particularly, target 77, the method can predict a substantial portion of a rare or even a novel fold. However, the current method still fails on some beta proteins, proteins over the 110-residue threshold, and sequences in which only a poor multiple sequence alignment can be built. On the other hand, for small proteins, the method gives results of quality at least similar to that of threading, with the advantage of not being restricted to known folds in the protein database. Overall, these results indicate that some progress has been made on the ab initio protein folding problem. Detailed information about our results can be obtained by connecting to http:/(/)www.bioinformatics.danforthcenter.org/+ ++CASP3.}, keywords = {Algorithms, Amino Acid Sequence, Evolution, Models, Molecular, Molecular Sequence Data, Monte Carlo Method, Protein Folding, Proteins, Proteins: chemistry}, issn = {0887-3585}, url = {http://www.ncbi.nlm.nih.gov/pubmed/10526366}, author = {Angel. R. Ortiz and Andrzej Koli{\'n}ski and Piotr Rotkiewicz and Bartosz Ilkowski and Jeffrey Skolnick} } @article {Kolinski1999a, title = {A method for the improvement of threading-based protein models}, journal = {Proteins}, volume = {37}, number = {4}, year = {1999}, month = {dec}, pages = {592{\textendash}610}, abstract = {A new method for the homology-based modeling of protein three-dimensional structures is proposed and evaluated. The alignment of a query sequence to a structural template produced by threading algorithms usually produces low-resolution molecular models. The proposed method attempts to improve these models. In the first stage, a high-coordination lattice approximation of the query protein fold is built by suitable tracking of the incomplete alignment of the structural template and connection of the alignment gaps. These initial lattice folds are very similar to the structures resulting from standard molecular modeling protocols. Then, a Monte Carlo simulated annealing procedure is used to refine the initial structure. The process is controlled by the model{\textquoteright}s internal force field and a set of loosely defined restraints that keep the lattice chain in the vicinity of the template conformation. The internal force field consists of several knowledge-based statistical potentials that are enhanced by a proper analysis of multiple sequence alignments. The template restraints are implemented such that the model chain can slide along the template structure or even ignore a substantial fraction of the initial alignment. The resulting lattice models are, in most cases, closer (sometimes much closer) to the target structure than the initial threading-based models. All atom models could easily be built from the lattice chains. The method is illustrated on 12 examples of target/template pairs whose initial threading alignments are of varying quality. Possible applications of the proposed method for use in protein function annotation are briefly discussed.}, keywords = {Amino Acid Sequence, Computer Simulation, Evaluation Studies as Topic, Methods, Models, Molecular, Molecular Sequence Data, Protein Conformation, Protein Structure, Proteins, Proteins: chemistry, Secondary, Sequence Alignment, Software Design}, issn = {0887-3585}, url = {http://www.ncbi.nlm.nih.gov/pubmed/10651275}, author = {Andrzej Koli{\'n}ski and Piotr Rotkiewicz and Bartosz Ilkowski and Jeffrey Skolnick} }