%0 Journal Article %J PLoS One %D 2012 %T The unique cysteine knot regulates the pleotropic hormone leptin. %A Haglund, Ellinor %A Joanna I. Sulkowska %A He, Zhao %A Feng, Gen-Sheng %A Jennings, Patricia A %A Onuchic, José N %K Cysteine %K Humans %K Kinetics %K Leptin %K MCF-7 Cells %K Models, Molecular %K Oxidation-Reduction %K Signal Transduction %X Leptin plays a key role in regulating energy intake/expenditure, metabolism and hypertension. It folds into a four-helix bundle that binds to the extracellular receptor to initiate signaling. Our work on leptin revealed a hidden complexity in the formation of a previously un-described, cysteine-knotted topology in leptin. We hypothesized that this unique topology could offer new mechanisms in regulating the protein activity. A combination of in silico simulation and in vitro experiments was used to probe the role of the knotted topology introduced by the disulphide-bridge on leptin folding and function. Our results surprisingly show that the free energy landscape is conserved between knotted and unknotted protein, however the additional complexity added by the knot formation is structurally important. Native state analyses led to the discovery that the disulphide-bond plays an important role in receptor binding and thus mediate biological activity by local motions on distal receptor-binding sites, far removed from the disulphide-bridge. Thus, the disulphide-bridge appears to function as a point of tension that allows dissipation of stress at a distance in leptin. %B PLoS One %V 7 %P e45654 %8 2012 %G eng %N 9 %R 10.1371/journal.pone.0045654 %0 Journal Article %J EPL (Europhysics Letters) %D 2011 %T Universal geometrical factor of protein conformations as a consequence of energy minimization %A Ming-Chya Wu %A Mai Suan Li %A Wen-Jong Ma %A Maksim Kouza %A Chin-Kun Hu %B EPL (Europhysics Letters) %V 96:68005 doi: 10.1209/0295-5075/96/68005 %G eng %R 10.1209/0295-5075/96/68005 %0 Journal Article %J Journal of the American Chemical Society %D 2010 %T Untying knots in proteins. %A Joanna I. Sulkowska %A Sułkowski, Piotr %A Szymczak, Piotr %A Cieplak, Marek %K Amino Acids %K Protein Conformation %K Proteins %X A shoelace can be readily untied by pulling its ends rather than its loops. Attempting to untie a native knot in a protein can also succeed or fail depending on where one pulls. However, thermal fluctuations induced by the surrounding water affect conformations stochastically and may add to the uncertainty of the outcome. When the protein is pulled by the termini, the knot can only get tightened, and any attempt at untying results in failure. We show that, by pulling specific amino acids, one may easily retract a terminal segment of the backbone from the knotting loop and untangle the knot. At still other amino acids, the outcome of pulling can go either way. We study the dependence of the untying probability on the way the protein is grasped, the pulling speed, and the temperature. Elucidation of the mechanisms underlying this dependence is critical for a successful experimental realization of protein knot untying. %B Journal of the American Chemical Society %V 132 %P 13954-6 %8 2010 Oct 13 %G eng %N 40 %R 10.1021/ja102441z %0 Journal Article %J Cell Cycle (Georgetown, Tex.) %D 2008 %T Uncharacterized DUF1574 leptospira proteins are SGNH hydrolases %A Lukasz Knizewski %A Kamil Steczkiewicz %A Krzysztof Kuchta %A Lucjan Wyrwicz %A Dariusz Plewczynski %A Andrzej Koliński %A Leszek Rychlewski %A Krzysztof Ginalski %K Amino Acid Sequence %K Bacterial Proteins %K Bacterial Proteins: genetics %K Base Sequence %K Computational Biology %K DNA %K Hydrolases %K Hydrolases: genetics %K Leptospira %K Leptospira: enzymology %K Models %K Molecular %K Molecular Sequence Data %K Sequence Alignment %K Sequence Analysis %B Cell Cycle (Georgetown, Tex.) %V 7 %P 542–4 %8 feb %G eng %U http://www.ncbi.nlm.nih.gov/pubmed/18235229 %0 Journal Article %J Bioinformatics (Oxford, England) %D 2008 %T Utility library for structural bioinformatics %A Dominik Gront %A Andrzej Koliński %K Computational Biology %K Computational Biology: methods %K Libraries %K Software %X In this Note we present a new software library for structural bioinformatics. The library contains programs, computing sequence- and profile-based alignments and a variety of structural calculations with user-friendly handling of various data formats. The software organization is very flexible. Algorithms are written in Java language and may be used by Java programs. Moreover the modules can be accessed from Jython (Python scripting language implemented in Java) scripts. Finally, the new version of BioShell delivers several utility programs that can do typical bioinformatics task from a command-line level. Availability The software is available for download free of charge from its website: http://bioshell.chem.uw.edu.pl. This website provides also numerous examples, code snippets and API documentation. %B Bioinformatics (Oxford, England) %V 24 %P 584–5 %8 feb %G eng %U http://www.ncbi.nlm.nih.gov/pubmed/18227118 %R 10.1093/bioinformatics/btm627 %0 Journal Article %J Biophysical Journal %D 2003 %T Unfolding of globular proteins: monte carlo dynamics of a realistic reduced model %A Andrzej Koliński %A Piotr Klein %A Piotr Romiszowski %A Jeffrey Skolnick %K Apoproteins %K Apoproteins: chemistry %K Bacterial Proteins %K Chemical %K DNA-Binding Proteins %K DNA-Binding Proteins: chemistry %K Leghemoglobin %K Leghemoglobin: chemistry %K Models %K Molecular %K Monte Carlo Method %K Myoglobin %K Myoglobin: chemistry %K Nerve Tissue Proteins %K Nerve Tissue Proteins: chemistry %K Plastocyanin %K Plastocyanin: chemistry %K Protein Denaturation %K Protein Folding %K Proteins %K Proteins: chemistry %K Statistical %X Reduced lattice models of proteins and Monte Carlo dynamics were used to simulate the initial stages of the unfolding of several proteins of various structural types, and the results were compared to experiment. The models semiquantitatively reproduce the approximate order of events of unfolding as well as subtle mutation effects and effects resulting from differences in sequences of similar folds. The short-time mobility of particular residues, observed in simulations, correlates with the crystallographic temperature factor. The main factor controlling unfolding is the native state topology, with sequence playing a less important role. The correlation with various experiments, especially for sequence-specific effects, strongly suggests that properly designed reduced models of proteins can be used for qualitative studies (or prediction) of protein unfolding pathways. %B Biophysical Journal %V 85 %P 3271–3278 %8 nov %G eng %U http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1303603&tool=pmcentrez&rendertype=abstract %R 10.1016/S0006-3495(03)74745-6 %0 Journal Article %J Biopolymers %D 2003 %T Use of residual dipolar couplings as restraints in ab initio protein structure prediction %A Turkan Haliloglu %A Andrzej Koliński %A Jeffrey Skolnick %K ab initio structure prediction %K dynamic modes %K residual dipolar coupling %K sicho model %X NMR residual dipolar couplings (RDCs), in the form of the projection angles between the respective internuclear bond vectors, are used as structural restraints in the ab initio structure prediction of a test set of six proteins. The restraints are applied using a recently developed SICHO (SIde-CHain-Only) lattice protein model that employs a replica exchange Monte Carlo (MC) algorithm to search conformational space. Using a small number of RDC restraints, the quality of the predicted structures is improved as reflected by lower RMSD/dRMSD (root mean square distance root mean square deviation) values from the corresponding native structures and by the higher correlation of the most cooperative mode of motion of each predicted structure with that of the native structure. The latter, in particular, has possible implications for the structurebased functional analysis of predicted structures. %B Biopolymers %V 70 %P 548–562 %G eng %U http://onlinelibrary.wiley.com/doi/10.1002/bip.10511/full %0 Journal Article %J Advances in Chemical Physics %D 2002 %T A unified approach to the prediction of protein structure and function %A Jeffrey Skolnick %A Andrzej Koliński %B Advances in Chemical Physics %V 120 %P 131–192 %G eng %U http://books.google.com/books?hl=en&lr=&id=FBhtodr1Ei8C&oi=fnd&pg=PA131&dq=a+unified+approach+to+the+prediction+of+protein+structure+and+function&ots=Fo3gV4RieR&sig=hZW2mXWR2\_yKXTARCuukSOERnoY %0 Book Section %B Computational Methods for Protein Folding %D 2002 %T A unified approach to the prediction of protein structure and function %A Jeffrey Skolnick %A Andrzej Koliński %K ab initio folding %K atomic models %K biochemical function %K comparative models %K ligand identification %K low-resolution structures %K Protein Structure %K reduced models %K threading %K unified folding scheme %X The major focus of this review is to describe a unified approach to protein structure prediction that reduces to threading plus structure refinement when an example of the probe sequence is found; but if not, it incorporates information from weakly significant probe sequence-template structure matches and then does ab initio folding with the structural information gleaned from such matches. It has the advantage that it can predict a novel fold even though some of the information comes from threading on already solved structures. %B Computational Methods for Protein Folding %V 120 %G eng %R 10.1002/0471224421.ch4 %0 Journal Article %J International Journal of Spectroscopy %D 1994 %T The unexpectedly low sensitivity of the nitrogen NMR shieldings of covalent azides to solvent effects %A Michal Witanowski %A Wanda Sicinska %A Graham A. Webb %B International Journal of Spectroscopy %V 12 %P 25-29 %G eng