%0 Journal Article %J Protein Science, 29:211-222 %D 2020 %T Flexible docking of peptides to proteins using CABS-dock %A Mateusz Kurcinski %A Aleksandra E. Badaczewska-Dawid %A Michal Kolinski %A Andrzej Koliński %A Sebastian Kmiecik %K molecular modeling %K peptide drugs %K peptide therapeutics %K protein–peptide complex %K protein–peptide interactions %K structure prediction %X Molecular docking of peptides to proteins can be a useful tool in the exploration of the possible peptide binding sites and poses. CABS-dock is a method for protein–peptide docking that features significant conformational flexibility of both the peptide and the protein molecules during the peptide search for a binding site. The CABS-dock has been made available as a web server and a standalone package. The web server is an easy to use tool with a simple web interface. The standalone package is a command-line program dedicated to professional users. It offers a number of advanced features, analysis tools and support for large-sized systems. In this article, we outline the current status of the CABS-dock method, its recent developments, applications, and challenges ahead. %B Protein Science, 29:211-222 %G eng %U https://onlinelibrary.wiley.com/doi/abs/10.1002/pro.3771 %R 10.1002/pro.3771 %0 Journal Article %J Methods in Molecular Biology %D 2017 %T Fast and Accurate Accessible Surface Area Prediction Without a Sequence Profile %A Eshel Faraggi %A Maksim Kouza %A Yaoqi Zhou %A Andrzej Kloczkowski %X A fast accessible surface area (ASA) predictor is presented. In this new approach no residue mutation profiles generated by multiple sequence alignments are used as inputs. Instead, we use only single sequence information and global features such as single-residue and two-residue compositions of the chain. The resulting predictor is both highly more efficient than sequence alignment based predictors and of comparable accuracy to them. Introduction of the global inputs significantly helps achieve this comparable accuracy. The predictor, termed ASAquick, is found to perform similarly well for so-called easy and hard cases indicating generalizability and possible usability for de-novo protein structure prediction. The source code and a Linux executables for ASAquick are available from Research and Information Systems at http://mamiris.com and from the Battelle Center for Mathematical Medicine at http://mathmed.org %B Methods in Molecular Biology %V 1484 %P 127-136 %G eng %0 Conference Proceedings %B Proceedings of the International Work-conference on Bioinformatics and BIOmedical engineering (IWWBIO) in Granada, Spain, 195-201, arXiv:1605.09269 %D 2016 %T Flexible protein-peptide docking using CABS-dock with knowledge about the binding site %A Mateusz Kurcinski %A Maciej Ciemny %A Maciej Blaszczyk %A Andrzej Koliński %A Sebastian Kmiecik %X Despite considerable efforts, structural prediction of protein-peptide complexes is still a very challenging task, mainly due to two reasons: high flexibility of the peptides and transient character of their interactions with proteins. Recently we have developed an automated web server CABS-dock (http://biocomp.chem.uw.edu.pl/CABSdock), which conducts flexible protein-peptide docking without any knowledge about the binding site. Our method allows for full flexibility of the peptide, whereas the flexibility of the receptor is restricted to near native conformations considering the main chain, and full flexibility of the side chains. Performance of the CABS-dock server was thoroughly tested on a benchmark of 171 test cases, both bound and unbound. Evaluation of the obtained results showed overall good performance of the method, especially that no information of the binding site was used. From unsuccessful experiments we learned that the accuracy of docking might be significantly improved, if only little information of the binding site was considered. In fact, in real-life applications user typically has access to some data indicating the location and/or structure of the binding site. In the current work, we test and demonstrate the performance of the CABS-dock server with two new features. The first one allows to utilize the knowledge about receptor residue(s) constituting the binding site, and the second one allows to enforce the desired secondary structure on the peptide structure. Based on the given example, we observe significant improvement of the docking accuracy in comparison to the default CABS-dock mode. %B Proceedings of the International Work-conference on Bioinformatics and BIOmedical engineering (IWWBIO) in Granada, Spain, 195-201, arXiv:1605.09269 %G eng %0 Conference Proceedings %B IWBBIO 2014 (2nd International Work-Conference on Bioinformatics and Biomedical Engineering) %D 2014 %T Flexible docking of the fragment of the troponin I to the troponin C %A Jacek Wabik %A Mateusz Kurcinski %A Andrzej Koliński %X Most of the current docking procedures are focused on fine conformational adjustment of assembled complexes and fail to reproduce large-scale motions. Our approach based on the coarse-grained modeling of flexible macromolecules overcomes these limitations. CABSDock procedure used in this work employs coarse-grained model CABS – efficient and versatile tool for modeling of proteins structure, dynamics and interactions [1-4]. In this work CABSDock was used to model assembly process of troponin C(TnC) with the N-terminal helix of the troponin I(TnI). TnC/TnI binding was investigated for both cardiac and skeletal troponin. TnI fragment was modeled allowing its unbiased movement. Entire structure of TnC domain was also treated as fully flexible, although its motion was restricted to near-native conformations. Binding of the TnI fragment changed the orientation between both domains. This picture provides valuable insight into mechanistic description of troponin function. %B IWBBIO 2014 (2nd International Work-Conference on Bioinformatics and Biomedical Engineering) %C Granada, Spain %G eng %0 Journal Article %J Journal of Molecular Modeling %D 2012 %T Fast learning optimized prediction methodology (FLOPRED) for protein secondary structure prediction %A Saras Saraswathi %A Juan Luis Fernandez Martinez %A Andrzej Koliński %A Robert L. Jernigan %A Andrzej Kloczkowski %K knowledge-based potentials %K learning %K machine %K neural networks %K particle swarm optimization %K protein secondary structure prediction %X

Computational methods are rapidly gaining importance in the field of structural biology, mostly due to the explosive progress in genome sequencing projects and the large disparity between the number of sequences and the number of structures. There has been an exponential growth in the number of available protein sequences and a slower growth in the number of structures. There is therefore an urgent need to develop computational methods to predict structures and identify their functions from the sequence. Developing methods that will satisfy these needs both efficiently and accurately is of paramount importance for advances in many biomedical fields, including drug development and discovery of biomarkers. A novel method called fast learning optimized prediction methodology (FLOPRED) is proposed for predicting protein secondary structure, using knowledge-based potentials combined with structure information from the CATH database. A neural network-based extreme learning machine (ELM) and advanced particle swarm optimization (PSO) are used with this data that yield better and faster convergence to produce more accurate results. Protein secondary structures are predicted reliably, more efficiently and more accurately using FLOPRED. These techniques yield superior classification of secondary structure elements, with a training accuracy ranging between 83 % and 87 % over a widerange of hidden neurons and a cross-validated testing accuracy ranging between 81 % and 84 % and a segment overlap (SOV) score of 78 % that are obtained with different sets of proteins. These results are comparable to other recently published studies, but are obtained with greater efficiencies, in terms of time and cost.

%B Journal of Molecular Modeling %V 18 %P 4275–89 %G eng %U http://www.ncbi.nlm.nih.gov/pubmed/22562230 %R 10.1007/s00894-012-1410-7 %0 Journal Article %J The Journal of Physical Chemistry B %D 2012 %T Folding Simulations of the A and B Domains of Protein G %A Maksim Kouza %A Ulrich H. E. Hansmann %X We study wild type and mutants of the A and B domain of protein G using all-atom Go-models. Our data substantiate the usefulness of such simulation for probing the folding mechanism of proteins and demonstrate that multifunnel versions of such models also allow probing of more complicated funnel landscapes. In our case, such models reproduce the experimentally observed distributions of the GA98 and GB98 mutants which differ only by one residue but fold into different structures. They also reveal details on the folding mechanism in these two proteins. %B The Journal of Physical Chemistry B %V 116 %P 6645-6653 %G eng %U http://pubs.acs.org/doi/abs/10.1021/jp210497h %R 10.1021/jp210497h %0 Journal Article %J The Journal of Physical Chemistry B %D 2012 %T From coarse-grained to atomic-level characterization of protein dynamics: transition state for the folding of B domain of protein A %A Sebastian Kmiecik %A Dominik Gront %A Maksim Kouza %A Andrzej Koliński %K coarse-grained modeling %K molecular dynamics %K multiscale modeling %K protein dynamics %X Atomic-level molecular dynamics simulations are widely used for the characterization of the structural dynamics of proteins; however, they are limited to shorter time scales than the duration of most of the relevant biological processes. Properly designed coarse-grained models that trade atomic resolution for efficient sampling allow access to much longer time-scales. In-depth understanding of the structural dynamics, however, must involve atomic details. In this study, we tested a method for the rapid reconstruction of all-atom models from $\alpha$ carbon atom positions in the application to convert a coarse-grained folding trajectory of a well described model system: the B domain of protein A. The results show that the method and the spatial resolution of the resulting coarse-grained models enable computationally inexpensive reconstruction of realistic all-atom models. Additionally, by means of structural clustering, we determined the most persistent ensembles of the key folding step, the transition state. Importantly, the analysis of the overall structural topologies suggests a dominant folding pathway. This, together with the all-atom characterization of the obtained ensembles, in the form of contact maps, matches the experimental results well. %B The Journal of Physical Chemistry B %V 116 %P 7026–32 %8 jun %G eng %U http://www.ncbi.nlm.nih.gov/pubmed/22486297 %R 10.1021/jp301720w %0 Journal Article %J Journal of Computer-Aided Molecular Design %D 2008 %T Fast and accurate methods for predicting short-range constraints in protein models %A Dominik Gront %A Andrzej Koliński %K Algorithms %K Amino Acid Sequence %K Models %K Molecular %K Molecular Sequence Data %K Predictive Value of Tests %K Protein %K Proteins %K Proteins: chemistry %K Proteins: genetics %K Proteins: metabolism %K Sequence Analysis %K Software %X

Protein modeling tools utilize many kinds of structural information that may be predicted from amino acid sequence of a target protein or obtained from experiments. Such data provide geometrical constraints in a modeling process. The main aim is to generate the best possible consensus structure. The quality of models strictly depends on the imposed conditions. In this work we present an algorithm, which predicts short-range distances between Calpha atoms as well as a set of short structural fragments that possibly share structural similarity with a query sequence. The only input of the method is a query sequence profile. The algorithm searches for short protein fragments with high sequence similarity. As a result a statistics of distances observed in the similar fragments is returned. The method can be used also as a scoring function or a short-range knowledge-based potential based on the computed statistics.

%B Journal of Computer-Aided Molecular Design %V 22 %P 783–8 %G eng %U http://www.ncbi.nlm.nih.gov/pubmed/18415023 %R 10.1007/s10822-008-9213-8 %0 Journal Article %J Biophysical Journal %D 2008 %T Folding pathway of the b1 domain of protein G explored by multiscale modeling %A Sebastian Kmiecik %A Andrzej Koliński %K Chemical %K coarse-grained modeling %K Computer Simulation %K Models %K Molecular %K Molecular Dynamics Simulation %K Nerve Tissue Proteins %K Nerve Tissue Proteins: chemistry %K Nerve Tissue Proteins: ultrastructure %K Protein Conformation %K protein dynamics %K Protein Folding %K Protein Structure %K Tertiary %X The understanding of the folding mechanisms of single-domain proteins is an essential step in the understanding of protein folding in general. Recently, we developed a mesoscopic CA-CB side-chain protein model, which was successfully applied in protein structure prediction, studies of protein thermodynamics, and modeling of protein complexes. In this research, this model is employed in a detailed characterization of the folding process of a simple globular protein, the B1 domain of IgG-binding protein G (GB1). There is a vast body of experimental facts and theoretical findings for this protein. Performing unbiased, ab initio simulations, we demonstrated that the GB1 folding proceeds via the formation of an extended folding nucleus, followed by slow structure fine-tuning. Remarkably, a subset of native interactions drives the folding from the very beginning. The emerging comprehensive picture of GB1 folding perfectly matches and extends the previous experimental and theoretical studies. %B Biophysical Journal %I Elsevier %V 94 %P 726–36 %8 feb %G eng %U http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2186257&tool=pmcentrez&rendertype=abstract %R 10.1529/biophysj.107.116095 %0 Journal Article %J Biophys J %D 2005 %T Folding of the protein domain hbSBD %A Maksim Kouza %A C. Chang %A S. Hayryan %A T. Yu %A Mai Suan Li %A T. Huang %A C. Hu %X The folding of the alpha-helix domain hbSBD of the mammalian mitochondrial branched-chain alpha-ketoacid dehydrogenase complex is studied by the circular dichroism technique in absence of urea. Thermal denaturation is used to evaluate various thermodynamic parameters defining the equilibrium unfolding, which is well described by the two-state model with the folding temperature T(F) = 317.8 +/- 1.95 K and the enthalpy change DeltaH(G) = 19.67 +/- 2.67 kcal/mol. The folding is also studied numerically using the off-lattice coarse-grained Go model and the Langevin dynamics. The obtained results, including the population of the native basin, the free-energy landscape as a function of the number of native contacts, and the folding kinetics, also suggest that the hbSBD domain is a two-state folder. These results are consistent with the biological function of hbSBD in branched-chain alpha-ketoacid dehydrogenase. %B Biophys J %V 89 %P 3353-61 %G eng %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