@article {Kurcinski2010, title = {Theoretical study of molecular mechanism of binding TRAP220 coactivator to Retinoid X Receptor alpha, activated by 9-cis retinoic acid}, journal = {The Journal of Steroid Biochemistry and Molecular Biology}, volume = {121}, number = {1-2}, year = {2010}, month = {jul}, pages = {124{\textendash}9}, publisher = {Elsevier Ltd}, abstract = {

Study on molecular mechanism of conformational reorientation of RXR-alpha ligand binding domain is presented. We employed CABS{\textendash}a reduced model of protein dynamics to model folding pathways of binding 9-cis retinoic acid to apo-RXR molecule and TRAP220 peptide fragment to the holo form. Based on obtained results we also propose a sequential model of RXR activation by 9-cis retinoic acid and TRAP220 coactivator. Methodology presented here may be used for investigation of binding pathways of other NR/hormone/cofactor sets.

}, keywords = {Binding Sites, Cell Nucleus, Cell Nucleus: metabolism, Computer Simulation, Crystallography, Humans, Ligands, Mediator Complex Subunit 1, Mediator Complex Subunit 1: metabolism, Models, Molecular, Molecular Conformation, Peptides, Peptides: chemistry, Protein Binding, Protein Structure, Retinoid X Receptor alpha, Retinoid X Receptor alpha: metabolism, Tertiary, Theoretical, Tretinoin, Tretinoin: metabolism, X-Ray, X-Ray: methods}, issn = {1879-1220}, doi = {10.1016/j.jsbmb.2010.03.086}, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2906686\&tool=pmcentrez\&rendertype=abstract}, author = {Mateusz Kurcinski and Andrzej Koli{\'n}ski} } @article {Kurcinski2007a, title = {Hierarchical modeling of protein interactions}, journal = {Journal of Molecular Modeling}, volume = {13}, number = {6-7}, year = {2007}, month = {jul}, pages = {691{\textendash}698}, abstract = {A novel approach to hierarchical peptide-protein and protein-protein docking is described and evaluated. Modeling procedure starts from a reduced space representation of proteins and peptides. Polypeptide chains are represented by strings of alpha-carbon beads restricted to a fine-mesh cubic lattice. Side chains are represented by up to two centers of interactions, corresponding to beta-carbons and the centers of mass of the remaining portions of the side groups, respectively. Additional pseudoatoms are located in the centers of the virtual bonds connecting consecutive alpha carbons. These pseudoatoms support a model of main-chain hydrogen bonds. Docking starts from a collection of random configurations of modeled molecules. Interacting molecules are flexible; however, higher accuracy models are obtained when the conformational freedom of one (the larger one) of the assembling molecules is limited by a set of weak distance restraints extracted from the experimental (or theoretically predicted) structures. Sampling is done by means of Replica Exchange Monte Carlo method. Afterwards, the set of obtained structures is subject to a hierarchical clustering. Then, the centroids of the resulting clusters are used as scaffolds for the reconstruction of the atomic details. Finally, the all-atom models are energy minimized and scored using classical tools of molecular mechanics. The method is tested on a set of macromolecular assemblies consisting of proteins and peptides. It is demonstrated that the proposed approach to the flexible docking could be successfully applied to prediction of protein-peptide and protein-protein interactions. The obtained models are almost always qualitatively correct, although usually of relatively low (or moderate) resolution. In spite of this limitation, the proposed method opens new possibilities of computational studies of macromolecular recognition and mechanisms of assembly of macromolecular complexes.}, keywords = {Algorithms, Amino Acid Sequence, Amino Acids, Amino Acids: analysis, Carbon, Carbon: chemistry, Computer Simulation, Crystallography, Hydrogen Bonding, Models, Molecular, Monte Carlo Method, Peptides, Peptides: chemistry, Peptides: metabolism, Protein Binding, Protein Conformation, Protein Structure, Proteins, Proteins: chemistry, Proteins: metabolism, Secondary, Stereoisomerism, Theoretical, X-Ray}, issn = {0948-5023}, doi = {10.1007/s00894-007-0177-8}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17297609}, author = {Mateusz Kurcinski and Andrzej Koli{\'n}ski} } @article {Gront2007, title = {T-Pile{\textendash}a package for thermodynamic calculations for biomolecules}, journal = {Bioinformatics (Oxford, England)}, volume = {23}, number = {14}, year = {2007}, month = {jul}, pages = {1840{\textendash}1842}, abstract = {Molecular dynamics and Monte Carlo, usually conducted in canonical ensemble, deliver a plethora of biomolecular conformations. Proper analysis of the simulation data is a crucial part of biophysical and bioinformatics studies. Sequence alignment problem can be also formulated in terms of Boltzmann distribution. Therefore tools for efficient analysis of canonical ensemble data become extremely valuable. T-Pile package, presented here provides a user-friendly implementation of most important algorithms such as multihistogram analysis and reweighting technique. The package can be used in studies of virtually any system governed by Boltzmann distribution. AVAILABILITY: T-Pile can be downloaded from: http://biocomp.chem.uw.edu.pl/services/tpile. These pages provide a comprehensive tutorial and documentation with illustrative examples of applications. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, keywords = {Algorithms, Biophysics, Biophysics: methods, Computational Biology, Computational Biology: methods, Computers, Hot Temperature, Models, Molecular Conformation, Monte Carlo Method, Probability, Proteins, Proteins: chemistry, Software, Temperature, Theoretical, Thermodynamics}, issn = {1367-4811}, doi = {10.1093/bioinformatics/btm259}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17510173}, author = {Dominik Gront and Andrzej Koli{\'n}ski} } @article {Pokarowski2005, title = {Inferring ideal amino acid interaction forms from statistical protein contact potentials}, journal = {Proteins}, volume = {59}, number = {1}, year = {2005}, month = {apr}, pages = {49{\textendash}57}, abstract = {We have analyzed 29 different published matrices of protein pairwise contact potentials (CPs) between amino acids derived from different sets of proteins, either crystallographic structures taken from the Protein Data Bank (PDB) or computer-generated decoys. Each of the CPs is similar to 1 of the 2 matrices derived in the work of Miyazawa and Jernigan (Proteins 1999;34:49-68). The CP matrices of the first class can be approximated with a correlation of order 0.9 by the formula e(ij) = h(i) + h(j), 1 Protein modeling could be done on various levels of structural details, from simplified lattice or continuous representations, through high resolution reduced models, employing the united atom representation, to all-atom models of the molecular mechanics. Here I describe a new high resolution reduced model, its force field and applications in the structural proteomics. The model uses a lattice representation with 800 possible orientations of the virtual alpha carbon-alpha carbon bonds. The sampling scheme of the conformational space employs the Replica Exchange Monte Carlo method. Knowledge-based potentials of the force field include: generic protein-like conformational biases, statistical potentials for the short-range conformational propensities, a model of the main chain hydrogen bonds and context-dependent statistical potentials describing the side group interactions. The model is more accurate than the previously designed lattice models and in many applications it is complementary and competitive in respect to the all-atom techniques. The test applications include: the ab initio structure prediction, multitemplate comparative modeling and structure prediction based on sparse experimental data. Especially, the new approach to comparative modeling could be a valuable tool of the structural proteomics. It is shown that the new approach goes beyond the range of applicability of the traditional methods of the protein comparative modeling.

}, keywords = {Amino Acid Sequence, Animals, Carbon, Carbon: chemistry, Crystallography, Databases as Topic, Humans, Hydrogen Bonding, Mathematics, Models, Molecular, Molecular Sequence Data, Protein Conformation, Protein Structure, Proteins, Proteins: chemistry, Proteomics, Proteomics: methods, Tertiary, Theoretical, X-Ray}, issn = {0001-527X}, doi = {035001349}, url = {http://www.ncbi.nlm.nih.gov/pubmed/15218533}, author = {Andrzej Koli{\'n}ski} } @article {Vinals2002, title = {Numerical study of the entropy loss of dimerization and the folding thermodynamics of the GCN4 leucine zipper}, journal = {Biophysical Journal}, volume = {83}, number = {5}, year = {2002}, month = {nov}, pages = {2801{\textendash}2811}, abstract = {A lattice-based model of a protein and the Monte Carlo simulation method are used to calculate the entropy loss of dimerization of the GCN4 leucine zipper. In the representation used, a protein is a sequence of interaction centers arranged on a cubic lattice, with effective interaction potentials that are both of physical and statistical nature. The Monte Carlo simulation method is then used to sample the partition functions of both the monomer and dimer forms as a function of temperature. A method is described to estimate the entropy loss upon dimerization, a quantity that enters the free energy difference between monomer and dimer, and the corresponding dimerization reaction constant. As expected, but contrary to previous numerical studies, we find that the entropy loss of dimerization is a strong function of energy (or temperature), except in the limit of large energies in which the motion of the two dimer chains becomes largely uncorrelated. At the monomer-dimer transition temperature we find that the entropy loss of dimerization is approximately five times smaller than the value that would result from ideal gas statistics, a result that is qualitatively consistent with a recent experimental determination of the entropy loss of dimerization of a synthetic peptide that also forms a two-stranded alpha-helical coiled coil.}, keywords = {Biophysical Phenomena, Biophysics, Databases as Topic, Dimerization, DNA-Binding Proteins, DNA-Binding Proteins: chemistry, Entropy, Hot Temperature, Leucine Zippers, Models, Monte Carlo Method, Protein Folding, Protein Kinases, Protein Kinases: chemistry, Saccharomyces cerevisiae Proteins, Saccharomyces cerevisiae Proteins: chemistry, Temperature, Theoretical, Thermodynamics}, issn = {0006-3495}, doi = {10.1016/S0006-3495(02)75289-2}, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1302364\&tool=pmcentrez\&rendertype=abstract}, author = {Jorge Vi{\~n}als and Andrzej Koli{\'n}ski and Jeffrey Skolnick} } @article {Godzik1995, title = {Are proteins ideal mixtures of amino acids? Analysis of energy parameter sets}, journal = {Protein Science: a Publication of the Protein Society}, volume = {4}, number = {10}, year = {1995}, month = {oct}, pages = {2107{\textendash}2117}, abstract = {Various existing derivations of the effective potentials of mean force for the two-body interactions between amino acid side chains in proteins are reviewed and compared to each other. The differences between different parameter sets can be traced to the reference state used to define the zero of energy. Depending on the reference state, the transfer free energy or other pseudo-one-body contributions can be present to various extents in two-body parameter sets. It is, however, possible to compare various derivations directly by concentrating on the "excess" energy-a term that describes the difference between a real protein and an ideal solution of amino acids. Furthermore, the number of protein structures available for analysis allows one to check the consistency of the derivation and the errors by comparing parameters derived from various subsets of the whole database. It is shown that pair interaction preferences are very consistent throughout the database. Independently derived parameter sets have correlation coefficients on the order of 0.8, with the mean difference between equivalent entries of 0.1 kT. Also, the low-quality (low resolution, little or no refinement) structures show similar regularities. There are, however, large differences between interaction parameters derived on the basis of crystallographic structures and structures obtained by the NMR refinement. The origin of the latter difference is not yet understood.}, keywords = {Amino Acid Sequence, Amino Acids, Crystallography, Databases, Factual, Magnetic Resonance Spectroscopy, Mathematics, Models, Protein Conformation, Protein Folding, Proteins, Proteins: chemistry, Theoretical, Thermodynamics, X-Ray}, issn = {0961-8368}, doi = {10.1002/pro.5560041016}, url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2142984\&tool=pmcentrez\&rendertype=abstract}, author = {Adam Godzik and Andrzej Koli{\'n}ski and Jeffrey Skolnick} } @article {Skolnick1989, title = {Monte Carlo studies on equilibrium globular protein folding. II. Beta-barrel globular protein models}, journal = {Biopolymers}, volume = {28}, number = {6}, year = {1989}, month = {jun}, pages = {1059{\textendash}95}, abstract = {In the context of dynamic Monte Carlo simulations on a model protein confined to a tetrahedral lattice, the interplay of protein size and tertiary structure, and the requirements for an all-or-none transition to a unique native state, are investigated. Small model proteins having a primary sequence consisting of a central bend neutral region flanked by two tails having an alternating hydrophobic/hydrophilic pattern of residues are seen to undergo a continuous transition to a beta-hairpin collapsed state. On increasing the length of the tails, the beta-hairpin structural motif is found to be in equilibrium with a four-member beta-barrel. Further increase of the tail length results in the shift of the structural equilibrium to the four-member beta-barrel. The random coil to beta-barrel transition is of an all-or-none character, but while the central turn is always the desired native bend, the location of the turns involving the two external strands is variable. That is, beta-barrels having the external stands that are two residues out of register are also observed in the transition region. Introduction into the primary sequence of two additional regions that are at the very least neutral toward turn formation produces an all-or-none transition to the unique, native, four-member beta-barrel. Various factors that can augment the stability of the native conformation are explored. Overall, these folding simulations strongly indicate that the general rules of globular protein folding are rather robust{\textendash}namely, one requires a general pattern of hydrophobic/hydrophilic residues that allow the protein to have a well-defined interior and exterior and the presence of regions in the amino acid sequence that at the very least are locally indifferent to turn formation. Since no site-specific interactions between hydrophobic and hydrophilic residues are required to produce a unique four-member beta-barrel, these simulations strongly suggest that site specificity is involved in structural fine-tuning.}, keywords = {Algorithms, Models, Monte Carlo Method, Protein Conformation, Proteins, Theoretical}, issn = {0006-3525}, doi = {10.1002/bip.360280604}, url = {http://www.ncbi.nlm.nih.gov/pubmed/2730942}, author = {Jeffrey Skolnick and Andrzej Koli{\'n}ski and Robert Yaris} }