Article
Chemistry, Physical
Luis Gutierrez-Arzaluz, Jiangtao Jia, Chun Gu, Justyna Czaban-Jozwiak, Jun Yin, Osama Shekhah, Osman M. Bakr, Mohamed Eddaoudi, Omar F. Mohammed
Summary: Highly luminescent metal-organic frameworks have been gaining attention for their potential applications as sensors and light-emitting devices. By exploring exciton migration dynamics between linkers with different protonation states in MOFs, this study provides insights into improving light-harvesting MOF architectures.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Minhao Tang, Fengtao Zhang, Yanfei Zhao, Yuepeng Wang, Zhengang Ke, Ruipeng Li, Wei Zeng, Buxing Han, Zhimin Liu
Summary: This study presents a CO2-mediated base catalysis approach for the activation of triple bonds in ionic liquids, achieving hydration of triple bonds to carbonyl chemicals. The tetrabutylphosphonium 2-hydroxypyridine demonstrates high efficiency for hydration of nitrites and C–C bond-containing compounds under a CO2 atmosphere, providing excellent yields. This catalytic protocol is simple, green, and efficient, providing a novel way to access carbonyl compounds through triple bond hydration under mild and metal-free conditions.
Article
Chemistry, Multidisciplinary
Julia Kotschy, Benedikt Soeldner, Himanshu Singh, Suresh K. Vasa, Rasmus Linser
Summary: This study reports the experimental identification of internal microsecond-scale dynamics of a high-affinity ligand tightly bound to the enzyme human carbonic anhydrase II (hCAII), even within a crystalline lattice. The authors demonstrate the existence of ligand's rotamer jumps through both solution and solid-state NMR experiments, and gain further insights through molecular dynamics simulations. This experimental confirmation of rotameric jumps in bound ligands within proteins in solution or the crystalline state is significant for understanding host-guest interactions in biology and supra-molecular chemistry, and for facilitating medicinal chemistry in drug research.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Medicinal
Timofey V. Losev, Igor S. Gerasimov, Maria V. Panova, Alexey A. Lisov, Yana R. Abdyusheva, Polina V. Rusina, Eugenia Zaletskaya, Oleg V. Stroganov, Michael G. Medvedev, Fedor N. Novikov
Summary: Bioisosteres are molecules with different substituents but similar shapes. They are widely used in drug design to modify metabolism, bioavailability, and activity. However, predicting the affinity of bioisosteres with computational methods has been challenging due to their similarity to standard force fields. In this study, a quantum mechanical (QM)-cluster approach based on the GFN2-xTB method was developed and successfully applied to predict the biological activity change of H -> F bioisosteric replacements. The method showed superior accuracy compared to the ChemPLP scoring function and comparable to in vitro experiments, with a standard deviation of 0.60 kcal/mol.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Review
Biochemistry & Molecular Biology
Glen. E. E. Kellogg, Anna Marabotti, Francesca Spyrakis, Andrea Mozzarelli
Summary: The aim of computational biochemists, medicinal chemists, and structural biologists has been to develop tools that can decode the interaction between molecules, resulting in a variety of complex biomolecular assemblies. The software application HINT, based on LogP scores, has been successful in mimicking the interactions among various biomolecules and providing insights into their energetics. The extensive collaboration between Abraham, Kellogg, and the University of Parma has played a crucial role in testing HINT for different biomolecular interactions.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Chemistry, Inorganic & Nuclear
Maria L. Buil, Javier A. Cabeza, Miguel A. Esteruelas, Susana Izquierdo, Carlos J. Laglera-Gandara, Antonio Nicasio, Enrique Onate
Summary: The reaction of hexahydride OsH6(PiPr(3))(2) with a P,Ge,P-germylene-diphosphine leads to an osmium tetrahydride derivative with a Ge,P-chelate, serving as a bifunctional catalyst for formic acid dehydrogenation. The study reveals that hydrogen formation occurs exclusively on the coordination sphere of the metal center, while both the metal center and the sigma-donor Lewis acid cooperatively participate in CO2 release, which is the rate-determining step.
INORGANIC CHEMISTRY
(2021)
Article
Chemistry, Inorganic & Nuclear
Evangelos Pilichos, Annia Tubau, Saskia Speed, Merce Font-Bardia, Albert Escuer, Arnald Grabulosa, Julia Mayans
Summary: A new family of lanthanide compounds with different structures and properties have been synthesized using dppeO(2) as a ligand. The compounds exhibit a two-dimensional or one-dimensional structure depending on the lanthanide cation. Some of the compounds have magnetic or luminescent properties, and they can be used as structural probes or for specific applications.
DALTON TRANSACTIONS
(2023)
Article
Chemistry, Inorganic & Nuclear
Shuai Ma, Ting Zhang, Jiong-Peng Zhao, Zhong-Yi Liu, Fu-Chen Liu
Summary: By ion dilution in the compound, the QTM of Dy-III was suppressed and SIM behavior was enhanced, while the fluorescence emission of 8-hydroxyquinoline was weakened. This method can achieve the dual function of fluorescent thermometers and SIM materials.
DALTON TRANSACTIONS
(2021)
Article
Mathematics, Applied
Zhan Chen, Yuanzhen Shao
Summary: In the past decade, variational implicit solvation models (VISM) have been successful in predicting solvation energy. However, existing VISMs lack the uniqueness of an energy minimizing solute-solvent interface, hindering the study of important interface properties. To address this, a new constrained VISM is introduced and rigorously analyzed. The model examines the existence, uniqueness, and regularity of the energy minimizing interface, and derives a necessary condition for a sharp solute-solvent interface. Experimental validation and numerical implementation demonstrate accurate solvation energy calculations.
COMPUTERS & MATHEMATICS WITH APPLICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Quentin Duez, Paul Tinnemans, Johannes A. A. W. Elemans, Jana Roithova
Summary: We present a new approach to determine ligand exchange parameters based on electrospray ionization mass spectrometry (ESI-MS). This method allows for the quantitative investigation of the solution-phase equilibria by introducing isotopically labelled ligands to a solution of metal host and unlabelled ligands. Our ESI-MS approach provides rate constants and activation parameters for ligand dissociation in the solution, providing mechanistic insights that are not easily obtained from traditional solution-phase techniques.
Article
Chemistry, Inorganic & Nuclear
Shrinwantu Pal
Summary: In hydrogenation mediated by half-sandwich complexes of Rh, Cp*Rh(iii)-H intermediates play a critical role as hydride-delivery agents. In bipyridine-supported complexes, a unique transformation called 'Cp* non-innocence' gives rise to (Cp*H)Rh(i) intermediates, which are believed to have enhanced hydride-delivery capabilities. However, DFT calculations show that (Cp*H)Rh(i) intermediates do not compete with the conventional pathway involving Cp*Rh(iii)-H, but rather result in sequential hydrogenation of the Cp* framework, potentially leading to catalyst degradation. Therefore, caution is advised when considering the truly homogeneous nature of hydrogenation catalysis mediated by this popular class of complexes.
DALTON TRANSACTIONS
(2023)
Article
Biochemical Research Methods
Chenran Wang, Yang Chen, Yuan Zhang, Keqiao Li, Menghan Lin, Feng Pan, Wei Wu, Jinfeng Zhang
Summary: Protein ligand docking is a computational tool for predicting protein functions and screening drug candidates. In this study, a novel reinforcement learning approach called A3C was developed to address the challenging problem of protein ligand docking. The experimental results showed significant improvement in binding site prediction compared to a naive model.
BMC BIOINFORMATICS
(2022)
Review
Biochemistry & Molecular Biology
Enrico O. O. Purisima, Christopher R. R. Corbeil, Francis Gaudreault, Wanlei Wei, Christophe Deprez, Traian Sulea
Summary: Scoring functions are widely used in structure-based drug design to predict binding modes and estimate binding affinities. The Solvated Interaction Energy (SIE) is a broadly applicable scoring function that has been successfully used for virtual screening and discovery of small-molecule binders and optimization of known drugs. It has also shown comparable accuracy in predicting antibody-antigen relative binding affinities.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Chemistry, Medicinal
Georgios Iakovou, Stephen D. Laycock, Steven Hayward
Summary: Interactive docking allows users to guide and control the docking of biomolecules, beneficial for SBDD and educating students on biomolecular interactions. It introduces DockIT for VR, which models conformational changes within the receptor in real-time.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Bruno Gildo Dalla Vecchia Morales, Marlon Chaves dos Reis, Thales Junior de Souza Gomes, Nabia Azevedo Zeferino, George Azevedo de Oliveira, Fernando Berton Zanchi
Summary: The study focused on Batroxrhagin, the main component in Bothrops atrox venom, and identified 42 molecules similar to batimastat with better interaction energy. These compounds present justifiable evidence for future inhibition of Batroxrhagin.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Andre Fischer, Manuel Sellner, Santhosh Neranjan, Martin Smiesko, Markus A. Lill
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Pharmacology & Pharmacy
Charleen G. Don, Martin Smiesko
FRONTIERS IN PHARMACOLOGY
(2020)
Article
Plant Sciences
Jakob K. Reinhardt, Amy M. Zimmermann-Klemd, Ombeline Danton, Martin Smiesko, Carsten Gruendemann, Matthias Hamburger
JOURNAL OF NATURAL PRODUCTS
(2020)
Article
Biochemistry & Molecular Biology
Manuel Sellner, Andre Fischer, Charleen G. Don, Martin Smiesko
Summary: Research using molecular dynamics simulations and protein-protein docking revealed the mechanism of conformational changes between cytochrome P450 enzymes and cytochrome P450 reductase, as well as proposed new conformational transition mechanisms and structural mechanisms for susceptibility to redox states.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Andre Fischer, Gabriela Frehner, Markus A. Lill, Martin Smiesko
Summary: Thyroid hormone receptors (TRs) are crucial for human development, growth, and metabolism, and antagonists of TRs can effectively treat hyperthyroidism. Computational methods such as MD simulations provide valuable insights into ligand-induced conformational changes in nuclear receptors, which can be important for the development of novel therapeutics.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemistry & Molecular Biology
Andre Fischer, Manuel Sellner, Karolina Mitusinska, Maria Bzowka, Markus A. Lill, Artur Gora, Martin Smiesko
Summary: Research assessed the selectivity of 33 reported non-covalent inhibitors of SARS-CoV-2 M-pro against eight proteases and 16 anti-targets, revealing off-target binding of some compounds to multiple proteases and anti-targets, with a high risk especially in chymase and cathepsin G.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Andre Fischer, Florian Hauptli, Markus A. Lill, Martin Smiesko
Summary: The study found that BF-3 inhibitors are more suitable for combination with classical antiandrogens than AF-2 inhibitors. Classic antiandrogens can cause changes in helix-12 through structural adaptation, accompanied by an expansion of the orthosteric binding site.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Medicinal
Andre Fischer, Martin Smiesko, Manuel Sellner, Markus A. Lill
Summary: This study reviewed the medicinal chemistry literature to explore the importance of visual inspection in molecular docking for drug discovery. Through surveys and expert opinions, valuable insights into visually supported decision-making processes were provided.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Silvia G. Inderbinen, Michael Zogg, Manuel Kley, Martin Smiesko, Alex Odermatt
Summary: The study discovered a species-specific inhibition of 11 beta-HSD2 by azole antifungals, with human enzyme being most sensitive, while mouse and zebrafish enzymes showing weak inhibition. Structural differences in the C-terminal region and substrate binding pocket were identified as key factors contributing to the observed differences in sensitivity to the inhibitors. This information could aid in future evaluations of 11 beta-HSD2 inhibitors and in selecting appropriate animal models for efficacy and safety studies.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Andre Fischer, Martin Smiesko
Summary: This study investigates an allosteric site in Cytochrome P450 enzymes, finding it to be well conserved in the CYP2 family with the exception of CYP2E1, and observing an enlargement of ligand tunnels in certain members that facilitate ligand translocation. The research contributes to understanding ligand access phenomena and aids in estimating the selectivity of metabolic transformations using computational techniques.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Andre Fischer, Ferhat Bardakci, Manuel Sellner, Markus A. Lill, Martin Smiesko
Summary: ERR alpha, ERR beta, and ERR gamma are nuclear receptors that regulate metabolic processes in various tissues. They have been implicated as drug targets for important indications. This study used molecular dynamics and metadynamics simulations to investigate the ligand pathways of these receptors, revealing their distribution and their role in ligand translocation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Katarzyna Papaj, Patrycja Spychalska, Katarzyna Hopko, Patryk Kapica, Andre Fisher, Markus A. Lill, Weronika Bagrowska, Jakub Nowak, Katarzyna Szleper, Martin Smiesko, Anna Kasprzycka, Artur Gora
Summary: In this study, a small library of thionocarbamates, thiolocarbamates, sulfide, and disulfide were tested as potential lead compounds for SARS-CoV-2 Mpro drug design using the microscale thermophoresis technique. The identified binder from the thionocarbamates group showed high potential for future modifications to improve affinity and solubility. Computational studies highlighted the inadequacy of simple approaches and the necessity of more advanced methods to properly evaluate the affinity of potential SARS-CoV-2 Mpro binders.
Article
Pharmacology & Pharmacy
Silvia G. Inderbinen, Manuel Kley, Michael Zogg, Manuel Sellner, Andre Fischer, Jacek Kedzierski, Stephanie Boudon, Anton M. Jetten, Martin Smiesko, Alex Odermatt
Summary: ROR gamma t is a key protein that regulates immune responses, and impaired function may contribute to inflammatory and autoimmune diseases and promote skin cancer. Certain chemicals commonly used in cosmetics and body care products have been found to activate ROR gamma t and potentially worsen skin diseases. Further research is needed to assess the concentrations of these compounds in tissues and target cells, and their significance in activating ROR gamma t.
Article
Environmental Sciences
Verena N. Schreier, Christian Appenzeller-Herzog, Beat J. Bruschweiler, Birgit Geueke, Martin F. Wilks, Thomas J. Simat, Benoit Schilter, Martin Smiesko, Jane Muncke, Alex Odermatt, Nicolas Roth
Summary: This article presents a systematic evidence map (SEM) that aims to identify and organize existing knowledge clusters and associated gaps in hazard and exposure information of PET oligomers. The study intends to provide insights for chemical risk assessment and support future toxicity testing strategies and regulatory decision-making regarding PET oligomers.
ENVIRONMENT INTERNATIONAL
(2022)
Article
Multidisciplinary Sciences
Christina Lamers, Xiaoguang Xue, Martin Smiesko, Henri van Son, Bea Wagner, Nadja Berger, Georgia Sfyroera, Piet Gros, John D. Lambris, Daniel Ricklin
Summary: The authors provide molecular-level insight into the mode-of-action, target selectivity, and species specificity of the compstatin family of complement inhibitors, which entered the clinic in 2021.
NATURE COMMUNICATIONS
(2022)