
Frederic VellieuxCharles University in Prague | CUNI · 1st Faculty of Medicine
Frederic Vellieux
B.Sc., Ph.D., HdR
Senior researcher, 1st Fac. Medicine, Charles University Prague (C.R.). MedChem Lab. HEAD: PR. DR. ING. JAKUBEK (DOCENT)
About
89
Publications
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Introduction
Chemist & Crystallographer,
senior researcher, 1st Faculty of Medicine, Charles University in Prague, BIOCEV Vestec site
Additional affiliations
January 2016 - December 2018
Czech Academy of Sciences, Institute of Biotechnology
Position
- Support man (scientific man.)
September 1984 - March 1991
September 1984 - August 1988
Education
April 2006 - October 2006
September 1984 - August 1988
September 1980 - July 1984
Publications
Publications (89)
Mitochondrial dysregulation plays a significant role in the carcinogenesis. On the other hand, its destabilization strongly represses the viability and metastatic potential of cancer cells. Photodynamic and photothermal therapies (PDT and PTT) target mitochondria effectively, providing innovative and non-invasive anticancer therapeutic modalities....
Immune checkpoints regulate the immune system response. Recent studies suggest that flavonoids, known as phytoestrogens, may inhibit the PD-1/PD-L1 axis. We explored the potential of estrogens and 17 Selective Estrogen Receptor Modulators (SERMs) as inhibiting ligands for immune checkpoint proteins (CTLA-4, PD-L1, PD-1, and CD80). Our docking studi...
Targeting of epigenetic mechanisms, such as the hydroxymethylation of DNA, has been intensively studied, with respect to the treatment of many serious pathologies, including oncological disorders. Recent studies demonstrated that promising therapeutic strategies could potentially be based on the inhibition of the TET1 protein (ten-eleven translocat...
The mechanisms by which myelodysplastic syndrome (MDS) cells resist the effects of
hypomethylating agents (HMA) are currently the subject of intensive research. A better understanding of mechanisms by which the MDS cell becomes to tolerate HMA and progresses to acute myeloid leukemia (AML) requires the development of new cellular models. From MDS/...
COVID−19 is a pandemic respiratory disease caused by the SARS−CoV−2 coronavirus. The worldwide epidemiologic data showed higher mortality in males compared to females, suggesting a hypothesis about the protective effect of estrogens against severe disease progression with the ultimate end being patient's death. This article summarizes the current k...
Interleukin-6 (IL-6) is a cytokine with multifaceted effects playing a remarkable role in the initiation of the immune response. The increased level of this cytokine in the elderly seems to be associated with the chronic inflammatory setting of the microenvironment in aged individuals. IL-6 also represents one of the main signals in communication b...
Fluorescent dyes and probes have been of interest in the fields of chemistry and biology for a long time.
However, with more recent applications in advanced techniques, such as two-photon and super-resolution fluorescence microscopy, higher demands are being placed on physico-chemical properties of such compounds.
Another requirement is specific in...
Thioxo, Oxo, Seleno and diastereomeric cyclophosphamides containing 1,3,2-dioxaphosphorinane are prepared by a one-step chemical reaction. Their structural determination is carried out by means of Nuclear Magnetic Resonance NMR ( 31 P, 1 H, 13 C) and
High-Resolution Mass Spectroscopy (HRMS). The conformational study of diastereomeric products is de...
Introduding the services offered at the Centre of Molecular Structure
Introducing the services at the CMS (X-ray diffraction and X-ray scattering)
A humoristic view of life in central Europe, presentation delivered for the winter solstice / xmas / end of the year party at the IBT
Introduction of the CMS and progress in its development
Provide tools to analyze biological molecules, proteins, nucleic acids, important organics, their complexes, interactions, higher molecular systems-towards structural biology of the cell; Structural studies (crystallisation, X-ray diffraction, structural mass spec) Biophysical characterization
The tail of Caudovirales bacteriophages serves as an adsorption device, a host cell wall-perforating machine and a genome delivery pathway. In Siphoviridae, the assembly of the long and flexible tail is a highly cooperative and regulated process that is initiated from the proteins forming the distal tail tip complex. In Gram-positive infecting siph...
Research interests (in macromolecular crystallography): 1 – Proteins of medical interest; 2 – Methodology in order to tackle problems of increasing difficulty
Lanthanoid ions exhibit extremely large anomalous X-ray scattering at theirLIII absorption edge. They are thus well suited for anomalous diffraction experiments. A novel class of lanthanoid complexes has been developed that combines the physical properties of lanthanoid atoms with functional chemical groups that allow non-covalent binding to protei...
The structure of a 468 kDa peptidase complex from the hyperthermophile Pyrococcus horikoshii has been solved at 1.9 A resolution. The monomer contains the M42 peptidase typical catalytic domain, and a dimerization domain that allows the formation of dimers that assemble as a 12-subunit self-compartmentalized tetrahedron, similar to those described...
Lactate dehydrogenase (LDH) catalyzes the conversion of pyruvate to lactate with concomitant oxidation of NADH during the last step in anaerobic glycolysis. In the present study, we present a comparative biochemical and structural analysis of various LDHs adapted to function over a large temperature range. The enzymes were from Champsocephalus gunn...
Intense synchrotron radiation produces specific structural and chemical damage to crystalline proteins even at 100 K. Carboxyl groups of acidic residues (Glu, Asp) losing their definition is one of the major effects observed. Here, the susceptibilities to X-ray damage of acidic residues in tetrameric malate dehydrogenase from Haloarcula marismortui...
Cellular proteolysis involves large oligomeric peptidases that play key roles in the regulation of many cellular processes. The cobalt-activated peptidase TET1 from the hyperthermophilic Archaea Pyrococcus horikoshii (PhTET1) was found to assemble as a 12-subunit tetrahedron and as a 24-subunit octahedral particle. Both quaternary structures were s...
The crystal structure of the sulfolactate dehydrogenase from the hyperthermophilic and methanogenic archaeon Methanocaldococcus jannaschii was solved at 2.5 A resolution (PDB id. 1RFM). The asymmetric unit contains a tetramer of tight dimers. This structure, complexed with NADH, does not contain a cofactor-binding domain with 'Rossmann-fold' topolo...
The crystal structure of malate dehydrogenase from the hyperthermophilic archaeon Archeoglobus fulgidus, in complex with its cofactor NAD, was solved at 2.9A resolution. The crystal structure shows a compact homodimer with one coenzyme bound per subunit. The substrate binding site is occupied by a sulphate ion. In order to gain insight into adaptat...
3-D structure of trypanosomal Pyruvate Phosphate Dikinase, a "high-hanging fruit".
Presentation made at the 2003 annual ACA meeting (Covington, KY, July 26-31) concerning the difficult 3D structure determination of the enzyme Pyruvate Phosphate Dikinase from Trypanosoma brucei
The three-dimensional crystal structure of the (R207S, R292S) mutant of malate dehydrogenase from Haloarcula marismortui was solved at 1.95A resolution in order to determine the role of salt bridges and solvent ions in halophilic adaptation and quaternary structure stability. The mutations, located at the dimer-dimer interface, disrupt two inter-di...
The crystal structure of the glycosomal enzyme pyruvate phosphate dikinase from the African protozoan parasite Trypanosoma brucei has been solved to 3.0 A resolution by molecular replacement. The search model was the 2.3 A resolution structure of the Clostridium symbiosum enzyme. Due to different relative orientations of the domains and sub-domains...
The PPi-dependent glycosomal enzyme pyruvate phosphate dikinase (PPDK) from Trypanosoma brucei is expressed in the insect stage of the parasite. Its precise function there is still unclear, but the enzyme may catalyze the ‘reverse reaction’ of transfer of phosphate from phosphoenolpyruvate (PEP) to generate pyruvate as a means of scavenging large a...
Ferredoxin-NADP⁺ reductase (FNR) and its physiological electron donor ferredoxin (Fd) from the cyanobacterium Anabaena PCC7119 have been co-crystallized. The unit-cell parameters are a = b = 63.72, c = 158.02 Å and the space group is P212121. The crystal structure has been solved with 2.4 Å resolution synchrotron data by molecular replacement, anom...
Introductory course about cell, molecular and structural biology. Taught at the Japan Defense Academy, Yokosuka, Nov. 27 to Dec. 5, 2000.
Introductory course about cell, molecular and structural biology. Taught at the Japan Defense Academy, Yokosuka, Nov. 27 to Dec. 5, 2000.
A procedure, called PBR (phase-bias reduction), has been developed to properly refine heavy-atom derivatives and to generate less biased heavy-atom phases when these derivatives contain common heavy-atom sites. Two independent events are obtained by splitting the refinement and phasing calculations into two stages, the first in which one of the der...
A comparison has been made of two methods for electron-density map improvement by the introduction of atomicity, namely the iterative skeletonization procedure of the CCP4 program DM [Cowtan & Main (1993). Acta Cryst. D49, 148-157] and the pseudo-atom introduction followed by the refinement protocol in the program suite DEMON/ANGEL [Vellieux, Hunt,...
A well-known method of noise reduction in image processing is the addition of multiple, independent images of the same object to generate an improved, averaged image. Using this method, one can increase the signal-to-noise ratio by a factor of N1/2, when N-independent images are being averaged. The technique has been used with great success in the...
A simple algorithm is described for the identification of spatially contiguous regions in crystallographic envelopes. In a single pass through the grid points of the envelope map, the occupied points are assigned to a series of locally contiguous sets based on consideration of the connections within single voxels. A spatially contiguous region is i...
The three weighting schemes for structure-factor amplitudes used in macromolecular crystallography, and the products of these weighting schemes, have been analysed by comparison of the figures of merit to the cosine of the phase difference between the current phase estimate and the true phase, and by computation of the linear correlation coefficien...
The OMIT electron-density-map calculation is very effective in discovering errors in a macromolecular structure determination. A Fortran program called OMIT has been written to calculate such maps and an investigation has been carried out into which coefficients for the map calculation produce the best OMIT maps. Testing of the program on Savinase...
The crystal structure of the ferredoxin:NADP+ reductase (FNR) from the cyanobacterium Anabaena PCC 7119 has been determined at 2.6 A resolution by multiple isomorphous replacement and refined using 15.0 A to 1.8 A data, collected at 4 degrees C, to an R-factor of 0.172. The model includes 303 residues, the flavin adenine dinucleotide cofactor (FAD)...
The structure of the thermostable triosephosphate isomerase (TIM) from Bacillus stearothermophilus complexed with the competitive inhibitor 2-phosphoglycolate was determined by X-ray crystallography to a resolution of 2.8 A. The structure was solved by molecular replacement using XPLOR. Twofold averaging and solvent flattening was applied to improv...
A procedure has been developed for the computation of the cross rotation function in the initial step of molecular replacement. This procedure involves the truncation of the model Patterson map by means of an envelope which follows the shape of this Patterson. Test calculations carried out using bovine phospholipase A2 as the search model and a mut...
The three-dimensional crystal structure of the enzyme glyceraldehyde phosphate dehydrogenase from the kinetoplastid Trypanosoma brucei brucei has been determined at 3.2 A resolution from a 37% complete data set collected using the Laue method. The crystals used in the structure determination contain one and a half tetrameric enzyme molecules in the...
The DEMON/ANGEL suite of computer programs has been developed to carry out density modification by non-crystallographic symmetry-averaging, solvent-flattening and histogram-mapping techniques. This suite consists of programs that allow molecular envelopes to be defined and modified, non-crystallographic symmetry operators to be refined either withi...
Partial set of slides. Taught at several EMBO practical courses, including in Heidelberg (1993)
Manuscript describing work on map-improvement by non-crystallographic symmetry averaging, the practical problems encountered and how to solve them. Further, the implementation of NCS averaging in the DEMON program suite is described. This paper formed the basis of a chapter published in Methods in Enzymology (vol. 277, pp 18-53, 1997). The subject...
The three-dimensional structure of glycosomal glyceraldehyde-3-phosphate dehydrogenase [D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.12.1.12] from the sleeping-sickness parasite Trypanosoma brucei was solved by molecular replacement at 3.2-A resolution with an x-ray data set collected by the Laue method. For data collect...
The three-dimensional structure of the quinoprotein methylamine dehydrogenase from Paracoccus dentrificans (PD-MADH) has been determined at 2.8 A resolution by the molecular replacement method combined with map averaging procedures, using data collected from an area detector. The structure of methylamine dehydrogenase from Thio-bacillus versutus, w...
The crystal structure of the complex between the quinoprotein methylamine dehydrogenase (MADH) and the type I blue copper protein amicyanin, both from Paracoccus denitrificans, has been determined at 2.5-A resolution using molecular replacement. The search model was MADH from Thiobacillus versutus. The amicyanin could be located in an averaged elec...
A model of tryptophan tryptophylquinone (TTQ), recently proposed by McIntire et al. (Science (1991) 252, 817-824) to be the prosthetic group of the quinoprotein methylamine dehydrogenase, has been compared with electron density maps of this dehydrogenase from Thiobacillus versutus and Paracoccus denitrificans. The comparison shows that the TTQ mode...
The protozoan haemoflagellate Trypanosoma brucei has two NAD‐dependent glyceraldehyde‐3‐phosphate dehydrogenase isoenzymes, each with a different localization within the cell. One isoenzyme is found in the cytosol, as in other eukaryotes, while the other is found in the glycosome, a microbody‐like organelle that fulfils an essential role in glycoly...
The crystal structure of quinoprotein methylamine dehydrogenase from Thiobacillus versutus (EC 1.4.99.3, Mr = 123,500) has been solved to 2.25 A resolution. The crystals of space group P3(1)21 (a = b = 129.8, c = 104.3 A) contain half a tetrameric enzyme molecule in the asymmetric unit, with a solvent content of ca 70%. The procedure used to solve...
The three-dimensional structure of quinoprotein methylamine dehydrogenase from Thiobacillus versutus has been determined at 2.25 A resolution by a combination of multiple isomorphous replacement, phase extension by solvent flattening and partial structure phasing using molecular dynamics refinement. In the resulting map, the polypeptide chain for b...
A model for the pro-PQQ cofactor of Thiobacillus versutus methylamine dehydrogenase was fitted into a 2.25 Å resolution electron density distribution for this enzyme. This proposed model of pro-PQQ consists of a tyrosine-derived quinone indole bicyclic structure. Linkage of the cofactor to the light subunit of the enzyme occurs via the side chain o...
The enzyme methylamine dehydrogenase or primary-amine:(acceptor) oxidoreductase (deaminating) (EC 1.4.99.3) was purified from the bacterium Thiobacillus versutus to homogeneity, as judged by polyacrylamide gel electrophoresis. The native enzyme has a Mr of 123 500 and contains four subunits arranged in a alpha 2 beta 2 configuration, the light and...
Questions
Questions (5)
Hi folks, I am a protein crystallographer. A colleague of mine (chemist) obtained some processed diffraction data together with a "SHELXS" solution. So she turned to me for help to follow this up. Last time I used shelx software, the programs were on punched cards with the diffraction data also on punched cards, immediately following the program. Atom cards were also on punched cards. Things have changed a bit since then.
I have tried to get some software (GUI software) on a Windows computer (I am a Unix person myself).
WingX installed fine but comes without the SHELX software. I failed to see where I could download the installer file(s) for SHELX programs. So WingX is totally useless without the crystallographic software that it is supposed to launch.
The SHELX programs are provided as executable for Linux. The Linux GUI only runs on Debian systems and I have Alma Linux, so no Linux GUI for me.
I am trying to follow instructions for running a refinement job in command line mode. The very first refinement job fails with the cryptic message:
** BAD ATOM OR UNKNOWN INSTRUCTION **
The .ins file I am trying to feed SHELXL with contains:
TITL 240223Ru_complex_0m_5 in P1
CELL 1.34139 10.36240 11.17780 13.19300 80.8589 73.7519 71.3166
ZERR 2.00 0.00070 0.00080 0.00090 0.0026 0.0023 0.0023
LATT -1
SFAC C H N O CL RU
UNIT 62 64 2 10 2 2
TEMP -163.150
TREF
L.S. 10 0 0
ACTA
BOND $H
CONF
HTAB
FMAP 2
PLAN 10
FVAR 1.00000
RU1 6 0.9211 0.1642 0.2141 11.000000 0.05
RU2 6 1.7758 0.0405 0.8871 11.000000 0.05
RU3 6 0.7840 0.0240 0.3064 11.000000 0.05
C1 1 1.9216 0.1409 0.6339 11.000000 0.051
C3 1 1.6386 -0.0790 0.5605 11.000000 0.058
C4 1 1.0572 0.2820 0.5423 11.000000 0.051
...
...
O94 4 1.2966 0.1878 0.1969 11.000000 0.058
C95 1 0.9826 0.0214 0.3655 11.000000 0.053
C96 1 0.9403 -0.0219 0.3468 11.000000 0.059
O101 4 2.3256 -0.3645 0.7462 11.000000 0.059
HKLF 4
END
Could anyone tell me what's going wrong? Or point me to an electronic bulletin board where I could ask the question? Thanks.
Hi,
We have to perform MD simulations on a limited number of protein:ligand complexes.
Since we aren't MD specialists we are trying to use charmm-gui.org to make the work easier.
The input pdb file contains protein + ligand coordinates. We have produced a .mol2 file using https://www.cheminfo.org/Chemistry/Cheminformatics/FormatConverter/index.html
We also saw that sometimes there are problems with .mol2 files and there is a script that may solve these problems (sort_mol2_bonds.pl).
When running charmm-gui , Solution Builder, then the program fails every time at the stage of generate.pdb with this error message (whichever of the two .mol2 files is used, either coming out of OpenBabel or after running the sort_mol2_bonds.pl) : "skipped empty mol2 file".
The mol2 files we are using are not empty.
Hence the questions are: is charmm-gui broken somehow? Or is there a solution to this problem allowing us to perform MD simulations on these protein:ligand complexes?
Thanks in advance.
Folks:
I have tried to contact the BIOVIA DiscoveryStudio support team, somehow my browser does not allow me to open their "contact form".
I am trying to visualize and perform an analysis on a protein:smaller molecule complex. The smaller molecule happens to be a long peptide. Whatever I do with the PDB (change ATOM cards to HETATM, change residue names to PEP, UNK, LGD, introduce MODEL and ENDMDL cards) DiscoveryStudio indicates the input PDB file doesn't contain any ligand.
Would any on ResearchGate have an idea of how to specify that a part of a coordinate file is the ligand, so that DiscoveryStudio 2021 recognises it as such and allows me to proceed?
Thanks,
Fred.
Hi all, I was asked to provide figures of the electrostatic potential (mapped to a surface, such as a VdW surface) for several complex small molecules.
GaussView allows one to do that provided some calculations with Gaussian are performed first. With 2 of these molecules, Gaussian seems to go into an infinite calculation loop and after weeks of energy minimization I stopped the calculations.
The Avogadro software is supposed to do that (this is the information provided on the internet, including a detailed manual, i.e. a How To).
When I download and installed avogadro from avogadro.cc then the executable when invoked indicates (in the Surface calculation menu) that the calculation of electrostatic potential surfaces is not yet implemented.
Hence my question: how can I perofm the calculations and provide these pictures ? With proteins it is quite easy using Pymol and the suitable add-on. Apparently not so for much smaller systems (small organic molecules).
Hi folks, I was asked (for an on-going research project) to perform molecular dynamics runs and follow the trajectories of O2 molecules during this run.
1 - I managed to get an ensemble of starting O2 positions;
2 - these are incorporated in a PDB file containing protein, FAD cofactor, H2Os;
3 - I managed to get access to "Maestro", so that the incomplete side chains were completed and the missing loops were introduced. The termini were capped, the protein was reoriented and I know the size of the box centered around the protein where water plus Na+ and Cl- ions should be added. I had to add a single Cl- ion manually (using the Coot software) because I couldn't access Desmond together with Maestro.
This is as far as I managed to reach. I tried to get Gromacs to run and even the test cases didn't work in my hands. The requirements from the higher ups: no money should be paid, I must do it using either my Linux workstation or freely available tools, software, servers, whatever so that the cost is 0.
Any idea ? I have checked Amber: one has to pay; I have checked Gromacs (vide supra): never worked in my hands; I have checked Desmond: the version that uses Maestro as its front end is for payment only.
Hence how can I manage to proceed to perform these calculations knowing the requirements from the higher ups (it must cost nothing)? Thanks.