Slovenian National Institute of Chemistry

Ljubljana, Slovenia

Slovenian National Institute of Chemistry

Ljubljana, Slovenia

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Stare J.,Slovenian National Institute of Chemistry
RSC Advances | Year: 2017

This work addresses the sampling issue commonly accompanying the simulation of chemical reactions. Very often the sampling is severely limited by complexity of the phase space, possibly leading to poorly converged or inaccurate free energy profiles. We explored the factors governing the completeness of reaction path sampling for the rate limiting step of phenylethylamine oxidation by lumiflavin in the gas phase, a reaction important for the pharmacology of the central nervous system. The simulations utilize the free energy perturbation sampling technique together with the empirical valence bond methodology for the free energy calculations. The simplicity of the system allows for the acquisition of fully converged free energy profiles, even for simulation free of restraints. The bottleneck for convergence is in the noticeably poorer sampling statistics in the transition state region, which is resolved by performing sufficiently long simulation to ensure reversibility of all processes accompanying the reaction. In the present case, convergence is attained in microseconds of simulation, but the required simulation time generally depends on the complexity of the potential energy surface pertinent to the reaction. Accordingly, the use of restraints reduces the complexity of the phase space, decreasing the required time by about an order of magnitude. In the case of elementary nucleophilic substitution with even simpler potential energy surface convergence is reached already at a timescale of few nanoseconds. For related biomolecular reactions embedded in an enzyme, significantly longer simulation times may be needed, rendering the sampling problem exceedingly difficult and representing a challenge for advanced sampling techniques. Accordingly, suggestions are given for optimal simulation of biomolecular reactions based on the presently employed techniques and under the aforementioned limitations. © The Royal Society of Chemistry.


Likozar B.,Slovenian National Institute of Chemistry | Levec J.,University of Ljubljana
Fuel Processing Technology | Year: 2014

Detailed reaction kinetics of oil transesterification were studied based on mechanism and reaction scheme of individual triglyceride, diglyceride, monoglyceride, glycerol and fatty acid methyl ester containing different combinations of gadoleic, linoleic, linolenic, oleic, palmitic and stearic acids determined by high-performance liquid chromatography. Pre-exponential factors and activation energies were correlated with molecular structure in terms of chain lengths and double bonds by response surface models. The activation energies of forward reactions were 47-61 kJ mol- 1 with backward ones being 31-49 kJ mol- 1, depending on component structure. Mass transfer during initial emulsion phase was acknowledged by determining diffusivities, distribution coefficients, molar volumes, boiling points and viscosities of individual components. Model was validated for a wide range of temperatures, hydrodynamic conditions, dispersed and continuous phase ratios, and methanolysis catalyst concentrations. Rotational speed had the most profound influence on the duration of transport phenomena-limited region spanning the latter to 27 min upon use of 100 rpm. Economics of the process were finally evaluated in terms of alcoholysis cost and price breakdown. Proposed methodology may be usefully applied to transesterification syntheses employing heterogeneous catalysis and enzymes, as well as various renewable resources such as microalgae lipids, waste oils, bioethanol and biobutanol. © 2014 Elsevier B.V.


Konc J.,Slovenian National Institute of Chemistry | Janezic D.,Slovenian National Institute of Chemistry | Janezic D.,University of Primorska
Bioinformatics | Year: 2010

Motivation: Exploitation of locally similar 3D patterns of physico-chemical properties on the surface of a protein for detection of binding sites that may lack sequence and global structural conservation. Results: An algorithm, ProBiS is described that detects structurally similar sites on protein surfaces by local surface structure alignment. It compares the query protein to members of a database of protein 3D structures and detects with sub-residue precision, structurally similar sites as patterns of physicochemical properties on the protein surface. Using an efficient maximum clique algorithm, the program identifies proteins that share local structural similarities with the query protein and generates structure-based alignments of these proteins with the query. Structural similarity scores are calculated for the query protein's surface residues, and are expressed as different colors on the query protein surface. The algorithm has been used successfully for the detection of protein-protein, protein-small ligand and protein-DNA binding sites. Availability: The software is available, as a web tool, free of charge for academic users at http://probis.cmm.ki.si. Contact: dusa@cmm.ki.si. Supplementary information: Supplementary data are available at Bioinformatics online. © The Author(s) 2010. Published by Oxford University Press.


Konc J.,Slovenian National Institute of Chemistry | Janezic D.,University of Primorska
Nucleic Acids Research | Year: 2014

The ProBiS-ligands web server predicts binding of ligands to a protein structure. Starting with a protein structure or binding site, ProBiS-ligands first identifies template proteins in the Protein Data Bank that share similar binding sites. Based on the superimpositions of the query protein and the similar binding sites found, the server then transposes the ligand structures from those sites to the query protein. Such ligand prediction supports many activities, e.g. drug repurposing. The ProBiS-ligands web server, an extension of the ProBiS web server, is open and free to all users at http://probis.cmm.ki. si/ligands. © 2014 The Author(s).


Konc J.,Slovenian National Institute of Chemistry | Konc J.,U.S. National Institutes of Health | Janezic D.,University of Primorska
Current Opinion in Structural Biology | Year: 2014

While structural genomics resulted in thousands of new protein crystal structures, we still do not know the functions of most of these proteins. One reason for this shortcoming is their unique sequences or folds, which leaves them assigned as proteins of 'unknown function'. Recent advances in and applications of cutting edge binding site comparison algorithms for binding site detection and function prediction have begun to shed light on this problem. Here, we review these algorithms and their use in function prediction and pharmaceutical discovery. Finding common binding sites in weakly related proteins may lead to the discovery of new protein functions and to novel ways of drug discovery. © 2013 Elsevier Ltd.


Godec A.,Slovenian National Institute of Chemistry | Merzel F.,Slovenian National Institute of Chemistry
Journal of the American Chemical Society | Year: 2012

The hydrophobic effect (HE) is commonly associated with the demixing of oil and water at ambient conditions and plays the leading role in determining the structure and stability of biomolecular assembly in aqueous solutions. On the molecular scale HE has an entropic origin. It is believed that hydrophobic particles induce order in the surrounding water by reducing the volume of configuration space available for hydrogen bonding. Here we show with computer simulation results that this traditional picture, based on average structural features of hydration water, configurational properties of single water molecules, and up to pairwise correlations, is not correct. Analyzing collective fluctuations in water clusters we are able to provide a fundamentally new picture of HE based on pronounced many-body correlations affecting the switching of hydrogen bonds (HBs) between molecules. These correlations emerge as a nonlocal compensation of reduced fluctuations of local electrostatic fields in the presence of an apolar solute. We propose an alternative view which may also be formulated as a maximization principle: The electrostatic noise acting on water molecules is maximized under the constraint that each water molecule on average maintains as many HBs as possible. In the presence of the solute the maximized electrostatic noise is a result of nonlocal fluctuations in the labile HB network giving rise to strong correlations among at least up to four water molecules. © 2012 American Chemical Society.


Konc J.,Slovenian National Institute of Chemistry | Janezic D.,Slovenian National Institute of Chemistry
Nucleic Acids Research | Year: 2012

The ProBiS web server is a web server for detection of structurally similar binding sites in the PDB and for local pairwise alignment of protein structures. In this article, we present a new version of the ProBiS web server that is 10 times faster than earlier versions, due to the efficient parallelization of the ProBiS algorithm, which now allows significantly faster comparison of a protein query against the PDB and reduces the calculation time for scanning the entire PDB from hours to minutes. It also features new web services, and an improved user interface. In addition, the new web server is united with the ProBiS-Database and thus provides instant access to pre-calculated protein similarity profiles for over 29000 non-redundant protein structures. The ProBiS web server is particularly adept at detection of secondary binding sites in proteins. It is freely available at http://probis.cmm.ki.si/old-version, and the new ProBiS web server is at http://probis.cmm.ki.si. © 2012 The Author(s).


Randic M.,Slovenian National Institute of Chemistry
Chemical Physics Letters | Year: 2014

For a selection of smaller benzenoid hydrocarbons we calculated ring bond orders (RBO) by adding the Pauling bond orders for CC bonds forming individual benzene rings. The RBO show full parallelism with qualitative expectations based on Clar's intuitive sextet theory. The highest RBO values belong to sextets of a single Clar structure, intermediate values to 'migrating' sextets and the smallest values to the 'empty' rings, and rings involving essentially single CC bond. This novel quantitative upgrading of the Clar structural formulas of aromatic benzenoid hydrocarbons offers numerical characterization of individual benzene rings as fully aromatic, intermediate, and weakly aromatics. © 2014 Published by Elsevier B.V.


Randic M.,Slovenian National Institute of Chemistry
Chemical Physics Letters | Year: 2010

We consider calculation of induced currents of π-electrons over the molecular network when molecules are placed in a magnetic field. The approach is based on consideration of current contributions arising from conjugated circuits within each individual Kekulé valence structure. The calculation is illustrated for an isomer of coronene C 24H 12 for which ab initio computations of π-electron current densities are available. Agreement is found between the quantum chemical ab initio computations that make no assumptions on ring contributions and the graph theoretical models based on conjugated circuit currents. © 2010 Elsevier B.V. All rights reserved.


Mavri J.,Slovenian National Institute of Chemistry
Toxicology in vitro : an international journal published in association with BIBRA | Year: 2013

In this article we report calculations of the activation free energy for a chemical reaction between propylene oxide and DNA, in particular with the guanine at the N7 position. Calculations were performed using Hartree-Fock and MP2 methods in conjunction with flexible basis sets. The effects of solvation were considered using the Langevin dipoles and solvent reaction field methods. The calculated activation free energies are in good agreement with the experimental value of 25.36 kcal/mol. Moreover, the reactivities of a series of ultimate carcinogens of the epoxy type toward DNA are shown to be related to their carcinogenicities. Higher reactivity is generally associated with higher carcinogenicity, although transport properties, reactions with ultimate carcinogen scavengers, and the DNA correction mechanism are also very important. It is very likely that the window of reactivity rather than a high reactivity value is the relevant measure of carcinogenicity, since highly reactive ultimate carcinogens interact with water and proteins before they reach DNA. Copyright © 2012 Elsevier Ltd. All rights reserved.

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