%0 Journal Article %J Journal of Inorganic Biochemistry %D 2018 %T Synthesis, structural and antimicrobial studies of type II topoisomerase-targeted copper(II) complexes of 1,3-disubstituted thiourea ligands %A Anna Bielenica %A Aleksandra Drzewiecka-Antonik %A Paweł Rejmak %A Joanna Stefańska %A Michał Koliński %A Sebastian Kmiecik %A Bogdan Lesyng %A Marta Włodarczyk %A Piotr Pietrzyk %A Marta Struga %K Copper complexes %K DNA gyrase %K docking %K FTIR %K Thiourea %X A series of Cu(II) complexes of 3-(trifluoromethyl)phenylthiourea derivatives was synthesized. Their structural properties were investigated by spectroscopic techniques (infrared and electron paramagnetic resonance), as well as molecular modeling. All studied coordination compounds are mononuclear complexes containing two chelating ligands bonded to the metal cation via S and deprotonated N atoms. The new chelates were evaluated for their antimicrobial potency. The complex of 1-(3,4-dichlorophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea (3) presented the highest activity against Gram-positive pathogens, even stronger than the activity of its non-complexed counterpart and the reference drug. The compound also prevented the biofilm formation of methicillin-resistant and standard strains of staphylococcal cocci. The title derivatives were found to be effective inhibitors of DNA gyrase and topoisomerase IV isolated from Staphylococcus aureus. The binding modes of the ligand L3 with DNA gyrase and topoisomerase IV were presented. %B Journal of Inorganic Biochemistry %V 182 %P 61 - 70 %G eng %U http://www.sciencedirect.com/science/article/pii/S016201341730692X %R https://doi.org/10.1016/j.jinorgbio.2018.01.005 %0 Journal Article %J Journal of Computational Chemistry %D 1999 %T Assessing energy functions for flexible docking %A Michal Vieth %A Jonathan D. Hirst %A Andrzej Koliński %A Charles L. Brooks III %K docking %K dynamics %K energy functions %K Molecular %K scoring functions %K simulated annealing %X A good docking algorithm requires an energy function that is selective, in that it clearly differentiates correctly docked structures from misdocked ones, and that is efficient, meaning that a correctly docked structure can be identified quickly. We assess the selectivity and efficiency of a broad spectrum of energy functions, derived from systematic modifications of the CHARMM param19/toph19 energy function. In particular, we examine the effects of the dielectric constant, the solvation model, the scaling of surface charges, reduction of van der Waals repulsion, and nonbonded cutoffs. Based on an assessment of the energy functions for the docking of five different ligand–receptor complexes, we find that selective energy functions include a variety of distance-dependent dielectric models together with truncation of the nonbonded interactions at 8 Å. We evaluate the docking efficiency, the mean number of docked structures per unit of time, of the more selective energy functions, using a simulated annealing molecular dynamics protocol. The largest improvements in efficiency come from a reduction of van der Waals repulsion and a reduction of surface charges. We note that the most selective potential is quite inefficient, although a hierarchical approach can be employed to take advantage of both selective and efficient energy functions. %B Journal of Computational Chemistry %V 19 %P 1612–1622 %G eng %U http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1096-987X(19981115)19:14%3C1612::AID-JCC7%3E3.0.CO;2-M/abstract %N 14 %R 10.1002/(SICI)1096-987X(19981115)19:14<1612::AID-JCC7>3.0.CO;2-M