Papers by Michal Kolinski
International Journal of Molecular Sciences
Sixteen new Ciprofloxacin derivatives were designed and successfully synthesized. In an in silico... more Sixteen new Ciprofloxacin derivatives were designed and successfully synthesized. In an in silico experiment, lipophilicity was established for obtained compounds. All compounds were screened for antimicrobial activity using standard and clinical strains. As for Gram-positive hospital microorganisms, all tested derivatives were active. Measured MICs were in the range 1–16 µg/mL, confirming high antimicrobial potency. Derivative 12 demonstrated activity against all standard Gram-positive Staphylococci, within the range of 0.8–1.6 µg/mL and was confirmed as the leading structure with MICs 1 µg/mL for S. pasteuri KR 4358 and S. aureus T 5591 (clinical strains). All compounds were screened for their in vitro cytotoxic properties via the MTT method. Three of the examined compounds (3, 11 and 16) showed good activity against cancer cells, and in parallel were found not to be cytotoxic toward normal cells. Doxorubicin SI ranged 0.14–1.11 while the mentioned three ranged 1.9–3.4. Selected C...
International Journal of Biological Macromolecules, 2020
Molecules, 2021
One of the major challenges in the computational prediction of protein–peptide complexes is the s... more One of the major challenges in the computational prediction of protein–peptide complexes is the scoring of predicted models. Usually, it is very difficult to find the most accurate solutions out of the vast number of sometimes very different and potentially plausible predictions. In this work, we tested the protocol for Molecular Dynamics (MD)-based scoring of protein–peptide complex models obtained from coarse-grained (CG) docking simulations. In the first step of the scoring procedure, all models generated by CABS-dock were reconstructed starting from their original C-alpha trace representations to all-atom (AA) structures. The second step included geometry optimization of the reconstructed complexes followed by model scoring based on receptor–ligand interaction energy estimated from short MD simulations in explicit water. We used two well-known AA MD force fields, CHARMM and AMBER, and a CG MARTINI force field. Scoring results for 66 different protein–peptide complexes show that ...
International Journal of Molecular Sciences, 2021
Computational prediction of molecular structures of amyloid fibrils remains an exceedingly challe... more Computational prediction of molecular structures of amyloid fibrils remains an exceedingly challenging task. In this work, we propose a multi-scale modeling procedure for the structure prediction of amyloid fibrils formed by the association of ACC1-13 aggregation-prone peptides derived from the N-terminal region of insulin’s A-chain. First, a large number of protofilament models composed of five copies of interacting ACC1-13 peptides were predicted by application of CABS-dock coarse-grained (CG) docking simulations. Next, the models were reconstructed to all-atom (AA) representations and refined during molecular dynamics (MD) simulations in explicit solvent. The top-scored protofilament models, selected using symmetry criteria, were used for the assembly of long fibril structures. Finally, the amyloid fibril models resulting from the AA MD simulations were compared with atomic force microscopy (AFM) imaging experimental data. The obtained results indicate that the proposed multi-sca...
Springer Series on Bio- and Neurosystems, 2018
The knowledge of the three-dimensional structure of proteins is crucial for understanding many im... more The knowledge of the three-dimensional structure of proteins is crucial for understanding many important biological processes. Most of the biologically relevant protein systems are too large for classical, atomistic molecular modeling tools. In such cases, coarse-grained (CG) models offer various opportunities for efficient conformational sampling and thus prediction of the three-dimensional structure. A variety of CG models have been proposed, each based on a similar framework consisting of a set of conceptual components such as protein representation, force field, sampling, etc. In this chapter we discuss these components, highlighting ideas which have proven to be the most successful. As CG methods are usually part of multistage procedures, we also describe approaches used for the incorporation of homology data and all-atom reconstruction methods.
The structural description of peptide ligands bound to G protein-coupled receptors (GPCRs) is imp... more The structural description of peptide ligands bound to G protein-coupled receptors (GPCRs) is important for the discovery of new drugs and deeper understanding of the molecular mechanisms of life. Here we describe a three-stage protocol for the molecular docking of peptides to GPCRs using a set of different programs: (1) CABS-dock for docking fully flexible peptides; (2) PD2 method for the reconstruction of atomistic structures from C-alpha traces provided by CABS-dock and (3) Rosetta FlexPepDock for the refinement of protein-peptide complex structures and model scoring. We evaluated the proposed protocol on the set of 7 different GPCR-peptide complexes (including one containing a cyclic peptide) for which crystallographic structures are available. We show that CABS-dock produces high resolution models in the sets of top-scored models. These sets of models, after reconstruction to all-atom representation, can be further improved by Rosetta high-resolution refinement and/or minimizat...
European journal of medicinal chemistry, Jan 5, 2018
A total of 14 of 1,5-disubstituted tetrazole derivatives were prepared by reacting appropriate th... more A total of 14 of 1,5-disubstituted tetrazole derivatives were prepared by reacting appropriate thiourea and sodium azide in the presence of mercury (II) chloride and triethylamine. All compounds were evaluated in vitro for their antimicrobial activity. Derivatives 10 and 11 showed the highest inhibition against Gram-positive and Gram-negative strains (standard and hospital strains). The observed minimal inhibitory concentrations values were in the range of 1-208 μM (0.25-64 μg/ml). Inhibitory activity of 1,5-tetrazole derivatives 10 and 11 against gyrase and topoisomerase IV isolated from S. aureus was studied. Evaluation was supported by molecular docking studies for all synthesized derivatives and reference ciprofloxacin. Moreover, selected tetrazoles (2, 3, 5, 6, 8, 9, 10 and 11) were evaluated for their cytotoxicity. All tested compounds are non-cytotoxic against HaCaT and A549 cells (CC ≤ 60 μM).
Chemical reviews, Jul 22, 2016
The traditional computational modeling of protein structure, dynamics, and interactions remains d... more The traditional computational modeling of protein structure, dynamics, and interactions remains difficult for many protein systems. It is mostly due to the size of protein conformational spaces and required simulation time scales that are still too large to be studied in atomistic detail. Lowering the level of protein representation from all-atom to coarse-grained opens up new possibilities for studying protein systems. In this review we provide an overview of coarse-grained models focusing on their design, including choices of representation, models of energy functions, sampling of conformational space, and applications in the modeling of protein structure, dynamics, and interactions. A more detailed description is given for applications of coarse-grained models suitable for efficient combinations with all-atom simulations in multiscale modeling strategies.
The Open Structural Biology Journal, 2008
Molecular & Cellular Proteomics, 2015
The Journal of Physical Chemistry C, 2009
... Jan S. Jaworski* , Agnieszka Kosson , Sławomir Filipek , Michał Koli ski and ... thre... more ... Jan S. Jaworski* , Agnieszka Kosson , Sławomir Filipek , Michał Koli ski and ... three simplest carbonyl derivatives of triptindane (C 3v -tribenzo[3.3.3]propellane, T), namely 9-triptindanone (T1), 9,10-triptindanedione (T2), and 9,10,11-triptindanetrione (T3) (Chart ), it was ...
Computational Methods to Study the Structure and Dynamics of Biomolecules and Biomolecular Processes, 2014
Biophysical Journal, 2014
FEBS Journal, 2014
In the present study, we report on the structural features of the bacteriorhodopsin triple mutant... more In the present study, we report on the structural features of the bacteriorhodopsin triple mutant E9Q/E194Q/E204Q (3Glu) of bacteriorhodopsin by combining experimental and molecular dynamics (MD) approaches. In 3Glu mutant, Glu9, Glu194 and Glu204 residues located at the extracellular side of the protein were mutated altogether to glutamines. UV-visible and differential scanning calorimetry experiments served as diagnostic tools for monitoring the resistance against thermal stress of the active site and the tertiary structures of the 3Glu. The analyses of the UV-visible thermal difference spectra demonstrate that the spectral forms at room temperature and the thermal unfolding path differ in the wild-type bacteriorhodopsin and the 3Glu. Even with these spectral differences, the thermal unfolding of the active site occurs at rather similar melting temperatures in both proteins. A noteworthy consequence of the mutations is the altered two-dimensional packing revealed by the lack of the pre-transition peak in differential scanning calorimetry traces of 3Glu mutant, as previously detected in wild-type and the corresponding single mutants. The infrared spectroscopy data agree with the loss of paracrystalinity, illustrating a substantial conversion of αII to αI helical conformation in the 3Glu mutant. Molecular dynamics simulations show higher dynamics flexibility of most of the extracellular regions of 3Glu, which may account for the somewhat lower tertiary structural stability of the mutated protein. Finally, hydrogen bond analysis reveals that the mutated Glu194 and Glu204 residues create ~ 50% less hydrogen bonds with water molecules compared to wild-type bacteriorhodopsin. These results exemplify the role of the water hydrogen-bonding network for structural integrity and conformational flexibility of bacteriorhodopsin.
Proceedings of the National Academy of Sciences, 2010
The γ-secretase complex has a decisive role in the development of Alzheimer’s disease, in that it... more The γ-secretase complex has a decisive role in the development of Alzheimer’s disease, in that it cleaves a precursor to create the amyloid β peptide whose aggregates form the senile plaques encountered in the brains of patients. Γ-secretase is a member of the intramembrane-cleaving proteases which process their transmembrane substrates within the bilayer. Many of the mutations encountered in early onset familial Alzheimer’s disease are linked to presenilin 1, the catalytic component of γ-secretase, whose active form requires its endoproteolytic cleavage into N-terminal and C-terminal fragments. Although there is general agreement regarding the topology of the N-terminal fragment, studies of the C-terminal fragment have yielded ambiguous and contradictory results that may be difficult to reconcile in the absence of structural information. Here we present the first structure of the C-terminal fragment of human presenilin 1, as obtained from NMR studies in SDS micelles. The structure ...
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Papers by Michal Kolinski