@article {Latek2011, title = {CABS-NMR{\textendash}De novo tool for rapid global fold determination from chemical shifts, residual dipolar couplings and sparse methyl-methyl NOEs}, journal = {Journal of c\Computational Chemistry}, volume = {32}, number = {3}, year = {2011}, pages = {536{\textendash}44}, abstract = {Recent development of nuclear magnetic resonance (NMR) techniques provided new types of structural restraints that can be successfully used in fast and low-cost global protein fold determination. Here, we present CABS-NMR, an efficient protein modeling tool, which takes advantage of such structural restraints. The restraints are converted from original NMR data to fit the coarse grained protein representation of the C-Alpha-Beta-Side-group (CABS) algorithm. CABS is a Monte Carlo search algorithm that uses a knowledge-based force field. Its versatile structure enables a variety of protein-modeling protocols, including purely de novo folding, folding guided by restraints derived from template structures or, structure assembly based on experimental data. In particular, CABS-NMR uses the distance and angular restraints set derived from various NMR experiments. This new modeling technique was successfully tested in structure determination of 10 globular proteins of size up to 216 residues, for which sparse NMR data were available. Additional detailed analysis was performed for a S100A1 protein. Namely, we successfully predicted Nuclear Overhauser Effect signals on the basis of low-energy structures obtained from chemical shifts by CABS-NMR. It has been observed that utility of chemical shifts and other types of experimental data (i.e. residual dipolar couplings and methyl-methyl Nuclear Overhauser Effect signals) in the presented modeling pipeline depends mainly on size of a protein and complexity of its topology. In this work, we have provided tools for either post-experiment processing of various kinds of NMR data or fast and low-cost structural analysis in the still challenging field of new fold predictions.}, keywords = {Algorithms, Animals, Cattle, Magnetic Resonance Spectroscopy, Magnetic Resonance Spectroscopy: methods, Models, Molecular, Monte Carlo Method, Protein Conformation, Protein Folding, Proteins, Proteins: chemistry, S100 Proteins, S100 Proteins: chemistry}, issn = {1096-987X}, doi = {10.1002/jcc.21640}, url = {http://www.ncbi.nlm.nih.gov/pubmed/20806263}, author = {Dorota Latek and Andrzej Koli{\'n}ski} } @article {Latek2007, title = {Protein structure prediction: combining de novo modeling with sparse experimental data}, journal = {Journal of Computational Chemistry}, volume = {28}, number = {10}, year = {2007}, month = {jul}, pages = {1668{\textendash}76}, abstract = {Routine structure prediction of new folds is still a challenging task for computational biology. The challenge is not only in the proper determination of overall fold but also in building models of acceptable resolution, useful for modeling the drug interactions and protein-protein complexes. In this work we propose and test a comprehensive approach to protein structure modeling supported by sparse, and relatively easy to obtain, experimental data. We focus on chemical shift-based restraints from NMR, although other sparse restraints could be easily included. In particular, we demonstrate that combining the typical NMR software with artificial intelligence-based prediction of secondary structure enhances significantly the accuracy of the restraints for molecular modeling. The computational procedure is based on the reduced representation approach implemented in the CABS modeling software, which proved to be a versatile tool for protein structure prediction during the CASP (CASP stands for critical assessment of techniques for protein structure prediction) experiments (see http://predictioncenter/CASP6/org). The method is successfully tested on a small set of representative globular proteins of different size and topology, including the two CASP6 targets, for which the required NMR data already exist. The method is implemented in a semi-automated pipeline applicable to a large scale structural annotation of genomic data. Here, we limit the computations to relatively small set. This enabled, without a loss of generality, a detailed discussion of various factors determining accuracy of the proposed approach to the protein structure prediction.}, keywords = {Algorithms, Computer Simulation, Magnetic Resonance Spectroscopy, Models, Molecular, Protein Folding, Protein Structure, Proteins, Proteins: chemistry, Secondary, Software}, issn = {0192-8651}, doi = {10.1002/jcc.20657}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17342709}, author = {Dorota Latek and Dariusz Ekonomiuk and Andrzej Koli{\'n}ski} } @article {297, title = {NMR assignments of tryptophan residue in apo and holo LBD-rVDR}, journal = {Proteins}, volume = {61}, year = {2005}, month = {2005 Nov 15}, pages = {461-7}, abstract = {Binding sites in the full-length, ligand-binding domain of rat vitamin D receptor (LBD-rVDR) for an active hormone derived from vitamin D (1alpha,25-dihydroxyvitamin D(3)) and three of its C-2 substituted analogs were compared by nuclear magnetic resonance (NMR) spectroscopy. Specific residue labeled with [UL]-(15)N(2) Trp allowed assignment of the side-chain H(epsilon1) and N(epsilon1) resonances of the single tryptophan residue at position 282 in LBD-rVDR. Comparison of (1)H[(15)N] Heteronuclear Single Quantum Correlation (HSQC) spectra of apo and holo LBD-rVDR revealed that the position of the Trp282 H(epsilon1) and N(epsilon1) signals are sensitive to the presence of the ligand in the receptor cavity. Binding of the ligands to LBD-rVDR results in a shift of both Trp H(epsilon1) and N(epsilon1) resonances to lower frequencies. The results indicate that the interaction between the ligands and Trp282 is not responsible for differences in calcemic activity observed in vitamin D analogs.}, keywords = {Animals, Apoproteins, Binding Sites, Ligands, Magnetic Resonance Spectroscopy, Rats, Receptors, Calcitriol, Tryptophan, Vitamin D}, issn = {1097-0134}, doi = {10.1002/prot.20625}, author = {Wanda Sicinska and William M. Westler and Hector F. DeLuca} } @article {300, title = {Solvent polarity and hydrogen-bonding effects on the nitrogen NMR shieldings of N-nitrosamines and DFT calculations of the shieldings of C-, N-, and O-nitroso systems}, journal = {Journal of Magnetic Resonance}, volume = {164}, year = {2003}, month = {2003 Oct}, pages = {212-9}, abstract = {High-precision nitrogen NMR shieldings, bulk susceptibility corrected, are reported for dimethyl-N-nitrosamine (I) and diethyl-N-nitrosamine (II) in a variety of solvents which represent a wide range of solvent properties from the point of view of polarity as well as hydrogen bond donor and acceptor strength. The observed range of solvent-induced nitrogen shielding variations of (I) and (II) is significant for the amino-type nitrogens, up to about 16 ppm, and originates essentially from the deshielding effect of the increasing polarity of solvent. On the other side, the nitroso nitrogen shieldings reveal an even stronger response to solvent effects, within about 20 ppm, but in this case the increasing polarity and hydrogen bond donor strength of solvent produce enhanced shielding. DFT quantum-mechanical calculations using the GIAO/B3PW91/6-311++G** approach and geometry optimizations employing the same basis set and hybrid density functionals show an excellent correlation with the experimental data on C-, N-, and O-nitroso moieties and reproduce not only major changes but also most of the subtle variations in the experimental nitrogen shieldings of the nitroso systems as a whole. A combination of the calculations involving the corresponding N and O-protonated species and the trends observed in the solvent-induced nitrogen shielding variations shows clearly that the prime acceptor site for hydrogen bonding is the nitroso oxygen atom.}, keywords = {Algorithms, Binding Sites, Carbon, Computer Simulation, Hydrogen Bonding, Macromolecular Substances, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Conformation, Molecular Structure, Nitrogen, Nitrogen Isotopes, Nitrosamines, Nitroso Compounds, Oxygen, solutions, Solvents}, issn = {1090-7807}, author = {Michal Witanowski and Zenobia Biedrzycka and Wanda Sicinska and Zbigniew Grabowski} } @article {290, title = {2-Ethyl and 2-ethylidene analogues of 1alpha,25-dihydroxy-19-norvitamin D(3): synthesis, conformational analysis, biological activities, and docking to the modeled rVDR ligand binding domain.}, journal = {Journal of Medicinal Chemistry}, volume = {45}, year = {2002}, month = {2002 Aug 1}, pages = {3366-80}, abstract = {Novel 19-nor analogues of 1alpha,25-dihydroxyvitamin D(3) were prepared and substituted at C-2 with an ethylidene group. The synthetic pathway was via Wittig-Horner coupling of the corresponding A-ring phosphine oxides with the protected 25-hydroxy Grundmann{\textquoteright}s ketones. Selective catalytic hydrogenation of 2-ethylidene analogues provided the 2alpha- and 2beta-ethyl compounds. The 2-ethylidene-19-nor compounds with a methyl group from the ethylidene moiety in a trans relationship to the C(6)-C(7) bond (E-isomers) were more potent than the corresponding Z-isomers and the natural hormone in binding to the vitamin D receptor. Both geometrical isomers (E and Z) of (20S)-2-ethylidene-19-norvitamin D(3) and both 2alpha-ethyl-19-norvitamins (in the 20R- and 20S-series) have much higher HL-60 differentiation activity than does 1alpha,25-(OH)(2)D(3). Both E-isomers (20R and 20S) of 2-ethylidene vitamins are characterized by very high calcemic activity in rats. The three-dimensional structure model of the rat vitamin D receptor and the computational docking of four synthesized (20R)-19-norvitamin D(3) analogues into its binding pocket are also reported.}, keywords = {Animals, Binding Sites, Biological Transport, Calcitriol, Calcium, Cell Differentiation, Chromatography, High Pressure Liquid, HL-60 Cells, Humans, Intestinal Mucosa, Ligands, Magnetic Resonance Spectroscopy, Male, Models, Molecular, Molecular Conformation, Rats, Receptors, Calcitriol, Spectrophotometry, Ultraviolet, Structure-Activity Relationship, Swine}, issn = {0022-2623}, author = {Rafal R. Sicinski and Piotr Rotkiewicz and Andrzej Koli{\'n}ski and Wanda Sicinska and Jean M. Prahl and Connie M. Smith and Hector F. DeLuca} } @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} }