News

Yasser Ruiz-Blanco among the winners of the Creative Young Investigator Award

Yasser Award

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The CRC1279 congratulates the Creative Young Investigator Award Winners, among them is Yasser Ruiz-Blanco.

The Creative Young Investigators Award provides € 10,000 start-up funding to support innovative ideas from young researchers.

For more information follow the link

New Cover in The Journal of Organic Chemistry

carbeneCover2019

You can find more information here:

https://pubs.acs.org/toc/joceah/84/18

 

New Front Cover and Cover Profile in CHEMPHYSCHEM

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Front Cover:

https://onlinelibrary.wiley.com/toc/14397641/2019/20/13

Cover Profile:

https://onlinelibrary.wiley.com/doi/10.1002/cphc.201900597

New Cover in The Journal of Organic Chemistry

cover-11

 

You can find more information here:

https://pubs.acs.org/toc/joceah/84/12

 

New paper in Protein Science

July 2019: New paper in Protein Science

ProtDCal-Suite: A web server for the numerical codification and functional analysis of proteins.

Romero-Molina S, Ruiz-Blanco YB, Green JR, Sanchez-Garcia E

Abstract

A web server comprising a set of machine learning-based methods for studying proteins. The main module of ProtDCal-Suite is the ProtDCal software. ProtDCal translates the structural information of proteins into numerical descriptors that serve as input to machine-learning techniques. The ProtDCal-Suite server also incorporates a post-processing optional stage that allows ranking and filtering the obtained descriptors by computing their Shannon entropy values across the input set of proteins. ProtDCal's codification was used in the development of models for the prediction of specific protein properties. Thus, the other modules of ProtDCal-Suite are protein analysis tools implemented using ProtDCal's descriptors. Among them are PPI-Detect, for predicting the interaction likelihood of protein-protein and protein-peptide pairs, Enzyme Identifier, for identifying enzymes from amino acid sequences or 3D structures, and Pred-NGlyco, for predicting N-glycosylation sites. ProtDCal-Suite is freely accessible at https://protdcal.zmb.uni-due.de.

The Young Investigator Support Program of the CRC 1279 awards Yasser Ruiz-Blanco

New researchers joined the group

Marz 2018 : Dr. Sunil Kumar Tripathi and Dipl.-Chem Julio Cesar Vieyto Nuñez  joined the group. Welcome!. Visit their research profiles in our group page.

New paper and cover in Journal of Computational Chemistry

The extension of the cluster of excellence RESOLV is granted

Sept 2018: The extension of the excellence cluster RESOLV, in which Elsa Sanchez Garcia and Uwe Bovensiepen represent the UDE as Principal Investigators, is granted! Congratulations!

You can find more information here:

New Ph.D student has joined the group

Sept 2018 : Sandra Romero Molina joined the group as PhD student. Welcome!. Visit here her research profile in our group page.

News

June 2018 : Prof. Matthias Heyden, from the Arizona State University, joined our group as visiting professor. Welcome!

May 2018 : Amandeep joined the group for an internship. Welcome!

Feb 2018 : New cover page. Pandian's paper in Chemistry - A European Journal  is featured as cover page of that issue of the journal. A cover profile (link) was also published describing the motivation and main findings of this work. The paper is also featured in RESOLV news

Jan 2018 : Dr. Angela Rodriguez Serrano and Dr. Yasser Ruiz Blanco join the group as  postdoctoral researchers. Angela will investigate solvation processes in chemical and biological systems and Yasser will perform biomolecular simulations and implement new approaches for protein recognition. 

Dec 2017 :  Congratulations to Sumit for his collaborative research on a ligand targeting the dimerization interface of an adapter protein, which is accepted in ChemBioChem as Very Important Paper

Nov 2017 :  Dr. Joel Mieres Perez joins the group as post-doc. He will be using QM and QM/MM approaches for reactive intermediates and biomolecules. 

Oct 2017 : Congratulations to Sumit and Kenny for their multidisciplinary JACS paper on 14-3-3 protein-protein interactions.

Aug 2017 : New JACS paper on aryl(trifluoromethyl)carbenes.

Jun 2017 : Elsa has now been appointed to the professorship for Computational Biochemistry at the Faculty of Biology, University of Duisburg-Essen (UDE). News

Apr 2017 : Congratulations to Sumit and Kenny for their JACS  paper on molecular tweezers and Huntington exon-1.

Feb 2017 : Congratulations to Kenny for his new collaborative paper on DNA–protein complexes in Nat. Comm.

Sept 2015 : Congratulations to Elsa for receiving the prestigious “PLUS 3” grant from the Boehringer Ingelheim Foundation

Visiting professor

June 2018 : Prof. Matthias Heyden, from the Arizona State University, joined our group as visiting professor. Welcome!

New paper in Angewandte Chemie

May 2018 :  New paper in Angewandte Chemie on Optical Gap in Acenes

Evolution of the Optical Gap in the Acene Series: Undecacene

Shen, Bin; Tatchen, Jörg; Sanchez-Garcia, Elsa and Holger Bettinger

Abstract: Undecacene, the largest member of the acene family, was photogenerated in a polymer matrix under cryogenic conditions from a precursor with two α‐diketone bridges. The electronic absorption of undecacene extends into the NIR region, but the spectrum is dominated by two strong absorptions in the UV/Vis range. The HOMO–LUMO transition is continuously shifted to lower energies as the number of rings of the acene increases (E vs. 1/N, N=number of rings), which is in line with the strong electron correlation calculated by DFT/MRCI.

New intern

May 2018 : Amandeep joined the group for an internship. Welcome!

New paper on Supramolecular Tweezers

Oct 2017 : New paper on inhibition of beta amyloid toxicity in The Journal of Physical Chemistry B .

               

The Aβ1–42 dimer is the smallest oligomer of the 42-residue Aβ peptide (Aβ1–42), which is involved in Alzheimer’s disease. The molecular tweezer CLR01 is a synthetic molecule that selectively binds lysine and arginine residues to inhibit toxic aggregation of amyloidogenic peptides. Here, we performed replica exchange molecular dynamics simulations of Aβ1–42 in explicit water to study, at the molecular level, the effect of CLR01 binding to the lysine and arginine residues in the dimer. We found that CLR01 molecules encapsulate both lysine residues of each Aβ1–42 monomer while only establishing labile interactions with tharginine residues to inhibit toxic aggregation of amyloidogenic peptides. Here, we performed replica exchange molecular dynamics simulations of Aβ1–42 in explicit water to study, at the molecular level, the effect of CLR01 binding to the lysine and arginine residues in the dimer. We found that CLR01 molecules encapsulate both lysine residues of each Aβ1–42 monomer while only establishing labile interactions with the arginine residues. This encapsulation leads to the noncovalent disruption of inter- and intramolecular interactions involving the monomers. Additionally, the total β-sheet content in the Aβ1–42 dimer decreases because of this binding. With CLR03, a negative control molecule that shares the charged core of CLR01 but does not form inclusion complexes, Aβ1–42 dimer formation is observed, similar to the reference system without ligands. Our work allows establishing a molecular mechanism for the modulation of protein–protein interactions in Aβ1–42 by CLR01. This mechanism is characterized by an aggregation pathway driven by the encapsulation of lysine residues as well as by the secondary interactions of tweezers with the peptide units and with other CLR01 molecules.

New cover page

Feb 2018 : New paper in Chemistry - A European Journal  is featured as cover page of that issue of the journal. A cover profile (link) was also published describing the motivation and main findings of this work. The paper is also featured in RESOLV news

New Post-Docs joined the group

Jan 2018 : Dr. Angela Rodriguez Serrano and Dr. Yasser Ruiz Blanco join the group as  postdoctoral researchers. Angela will investigate solvation processes in chemical and biological systems and Yasser will perform biomolecular simulations and implement new approaches for protein recognition.Visit here their research profiles in our group page.

New very important paper

Dec 2017 :  New paper on a ligand targeting the dimerization interface of an adapter protein, is accepted in ChemBioChem as Very Important Paper.

Rational Design, Binding Studies, and Crystal-Structure Evaluation of the First Ligand Targeting the Dimerization Interface of the 14-3-3ζ Adapter Protein.

Ehlers, Martin; Grad, Jean-Noel; Mittal, Sumit; Bier, David; Mertel, Marcel; Ohl, Ludwig; Bartel, Maria; Briels, Jeroen; Heimann, Marius; Ottmann, Christian; Sanchez-Garcia, Elsa*; Hoffmann, Daniel* and Schmuck, Carsten*.

Abstract: 14‐3‐3 Proteins play a central role in signalling pathways in cells: they interact as gatekeeper proteins with a huge number of binding partners. Their function as hub for intracellular communication can explain why these adapter proteins are associated with a wide range of diseases. How they control the various cellular mechanisms is still unclear, but it is assumed that the dimeric nature of the 14‐3‐3 proteins plays a key role in their activity. Here, we present, to the best of our knowledge, the first example of a small molecule binding to the 14‐3‐3ζ dimerisation interface. This compound was designed by rational in silico optimisation of a peptidic ligand identified from biochemical screening of a peptidic library, and the binding was characterised by UV/Vis spectroscopy, microscale thermophoresis, multiscale simulations, and X‐ray crystallography.

New Post-Doc joined the group

Nov 2017 :  Dr. Joel Mieres Perez joins the group as post-doc. He will be using QM and QM/MM approaches for reactive intermediates and biomolecules. Visit here his research profile in our group page.

New paper in JACS

Oct 2017 : New paper in JACS on 14-3-3 protein-protein interactions.

Abstract:  We performed a comparative study on the interaction modes of 2‐haloimidazolium salts with anions in solution, particularly with regard to halogen bonding, hydrogen bonding and anion–π interactions. The syntheses and solid‐state analyses of a series of sterically and electronically modified 2‐haloimidazolium structures are presented. Detailed isothermal titration calorimetry (ITC) measurements, quantum mechanics/molecular mechanics (QM/MM), classical molecular dynamics simulations (MD) and free‐energy calculations together with NMR spectroscopy were used to elucidate the binding modes in solution. Our work reveals the absence of a potential anion–π interaction between the cationic imidazolium ring and the Lewis basic counteranion, and corroborates a formation of halogen bonding via the Lewis acidic iodine moiety and hydrogen bonding via the backbone hydrogen atoms, with repercussions in the field of organocatalysis.

New paper in JACS

Aug 2017 : New JACS paper on aryl(trifluoromethyl)carbenes.

the singlet state. This interconversion is thermally irreversible, and cooling back to 3 K does not change the singlet to triplet ratio. Irradiation at 365 nm results in a complete singlet to triplet interconversion, whereas 450 nm irradiation produces again up to 20% of the singlet state. An alternative way to generate the singlet carbene is the reaction of the triplet with water molecules by annealing water-doped matrices at 25 K.This results in the irreversible formation of a hydrogen-bonded complex between the singlet carbene and water. For fluorenyl(trifluoromethyl)carbene, very similar results are obtained, but the yield of the singlet state is even higher. Magnetic bistability of carbenes seems to be a general phenomenon that only depends on the singlet–triplet gap rather than on the nature of the carbene.

Professorship for Computational Biochemistry

Jun 2017 : Elsa has now been appointed to the professorship for Computational Biochemistry at the Faculty of Biology, University of Duisburg-Essen (UDE). News

New paper in JACS

Apr 2017 : New paper in  JACS on molecular tweezers and Huntington exon-1.

Abstract:  pHuntington’s disease is a neurodegenerative disorder associated with the expansion of the polyglutamine tract in the exon-1 domain of the huntingtin protein (htte1). Above a threshold of 37 glutamine residues, htte1 starts to aggregate in a nucleation-dependent manner. A 17-residue N-terminal fragment of htte1 (N17) has been suggested to play a crucial role in modulating the aggregation propensity and toxicity of htte1. Here we identify N17 as a potential target for novel therapeutic intervention using the molecular tweezer CLR01. A combination of biochemical experiments and computer simulations shows that binding of CLR01 induces structural rearrangements within the htte1 monomer and inhibits htte1 aggregation, underpinning the key role of N17 in modulating htte1 toxicity.

New paper in Nat. Comm.

Feb 2017 : New paper on DNA–protein complexes in Nat. Comm.

Tailored Protein Encapsulation into a DNA Host Using Geometrically Organized Supramolecular Interactions

Sprengel, Andreas; Lill, Pascal; Stegemann, Pierre; Bravo-Rodriguez, Kenny; Schöneweiß, Elisa-C.; Merdanovic, Melisa; Gudnason, Daniel; Aznauryan, Mikayel; Gamrad, Lisa; Barcikowski, Stephan; Sanchez-Garcia, Elsa; Birkedal, Victoria; Gatsogiannis, Christos; Ehrmann, Michael and Saccà,  Barbara.

Abstract: The self-organizational properties of DNA have been used to realize synthetic hosts for protein encapsulation. However, current strategies of DNA–protein conjugation still limit true emulation of natural host–guest systems, whose formation relies on non-covalent bonds between geometrically matching interfaces. Here we report one of the largest DNA–protein complexes of semisynthetic origin held in place exclusively by spatially defined supramolecular interactions. Our approach is based on the decoration of the inner surface of a DNA origami hollow structure with multiple ligands converging to their corresponding binding sites on the protein surface with programmable symmetry and range-of-action. Our results demonstrate specific host–guest recognition in a 1:1 stoichiometry and selectivity for the guest whose size guarantees sufficient molecular diffusion preserving short intermolecular distances. DNA nanocontainers can be thus rationally designed to trap single guest molecules in their native form, mimicking natural strategies of molecular recognition and anticipating a new method of protein caging.

New paper in Nat. Comm.

Oct 2016 : New paper on solvent interactions with carbenes in Nat. Comm.

Competitive Solvent-Molecule Interactions Govern the Primary Processes of Diphenylcarbene in Solvent Mixtures

Knorr, Johannes; Sokkar, Pandian; Schott, Sebastian; Costa, Paolo; Thiel, Walter; Sander, Wolfram;  Sanchez-Garcia, Elsa* and Nuernberger, Patrick*.

Abstract: Photochemical reactions in solution often proceed via competing reaction pathways comprising intermediates that capture a solvent molecule. A disclosure of the underlying reaction mechanisms is challenging due to the rapid nature of these processes and the intricate identification of how many solvent molecules are involved. Here combining broadband femtosecond transient absorption and quantum mechanics/molecular mechanics simulations, we show for one of the most reactive species, diphenylcarbene, that the decision-maker is not the nearest solvent molecule but its neighbour. The hydrogen bonding dynamics determine which reaction channels are accessible in binary solvent mixtures at room temperature. In-depth analysis of the amount of nascent intermediates corroborates the importance of a hydrogen-bonded complex with a protic solvent molecule, in striking analogy to complexes found at cryogenic temperatures. Our results show that adjacent solvent molecules take the role of key abettors rather than bystanders for the fate of the reactive intermediate.

New paper in JACS

2016 : New paper in  JACS on halogen bonding of carbenes

of DPC is observed. Thus, halogen bonding is a powerful new principle to control the spin state of reactive carbenes.

New paper in JACS

Jan 2016 : New paper in  JACS on magnetic bistability of carbenes

IR, UV–vis, and X-band EPR spectroscopy and in MTHF glasses by W-band EPR and Q-band ENDOR spectroscopy. UV (365 nm) irradiation of the system results in formation of predominantly the triplet carbene, whereas visible (450 nm) light shifts the photostationary equilibrium toward the singlet state. Upon annealing at higher temperatures (>10 K), the triplet is converted to the singlet; however, cooling back to 3 K does not restore the triplet. Therefore, depending on matrix temperature and irradiation conditions, matrices containing predominantly the triplet or singlet carbene can be generated. Controlling the magnetic and chemical properties of carbenes by using light of different wavelengths might be of general interest for applications such as information storage and radical-initiated polymerization processes.

Grant from the Boehringer Ingelheim Foundation

Sept 2015 : Congratulations to Elsa for receiving the prestigious “PLUS 3” grant from the Boehringer Ingelheim Foundation