Spatial arrangements of cyclodextrin host–guest complexes in solution studied by ¹³C NMR and molecular modelling

• Konstantin Lebedinskiy,
• Ivan Barvík,
• Zdeněk Tošner,
• Ivana Císařová,
• Jindřich Jindřich and
• Radim Hrdina

Beilstein J. Org. Chem. 2024, 20, 331–335, doi:10.3762/bjoc.20.33

• ten classical molecular dynamics (MD) simulations [16] (each lasting 100 ns, Figure 3). Then, we superimposed α-CD structures from different snapshots of each MD run. Further, the 3D densities, showing the spatial distribution of prochiral atoms of ligands (that rotate and wobble towards α-CD), were

Electron-beam-promoted fullerene dimerization in nanotubes: insights from DFT computations

• Laura Abella,
• Gerard Novell-Leruth,
• Josep M. Ricart,
• Josep M. Poblet and
• Antonio Rodríguez-Fortea

Beilstein J. Org. Chem. 2024, 20, 92–100, doi:10.3762/bjoc.20.10

• metadynamics simulations provide hints on structures for the initial steps of the irreversible phase 2 where bond formation and breaking lead to important structural reorganizations within the coalescence process. Keywords: DFT; dimerization; fullerene; molecular dynamics; peapods; Introduction Transmission

• pressures and high temperatures [13][14][15]. We aim to shed light in these reaction mechanisms and energy profiles by using complementary methodologies as standard density functional theory (DFT) calculations and first-principles Car–Parrinello molecular dynamics (CPMD) simulations. Firstly, we have

• surface that describes the formation of irreversible C–C bonds. Molecular dynamics simulations were done in the radical C120 dimer alone; we did not consider the interaction with the CNT. After a 4 ps metadynamics, we observed the sequential formation of C–C bonds between the two C60 cages up to a number

Studying specificity in protein–glycosaminoglycan recognition with umbrella sampling

• Mateusz Marcisz,
• Sebastian Anila,
• Margrethe Gaardløs,
• Martin Zacharias and
• Sergey A. Samsonov

Beilstein J. Org. Chem. 2023, 19, 1933–1946, doi:10.3762/bjoc.19.144

• explanation and prediction of GAG specificity [35]. Computational methodologies like molecular docking and molecular dynamics (MD) have proven to be successful in modelling protein–GAG interactions, particularly examining the fundamental questions related to these interactions such as their specificity, the

Complexes of resorcin[4]arene with secondary amines: synthesis, solvent influence on “in-out” structure, and theoretical calculations of non-covalent interactions

• Waldemar Iwanek

Beilstein J. Org. Chem. 2023, 19, 1525–1536, doi:10.3762/bjoc.19.109

• atoms, presenting a challenging and time-consuming task for geometry optimization calculations and screening via DFT methods. Recent advancements have introduced fast semi-empirical DFT methods such as xTB [15], which enable their use in preliminary screening for molecular dynamics or searching for

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• functions of ether lipids offer an interesting overview of the current knowledge of the effect of plasmalogen and ELs on membrane properties at a molecular scale. Shortly, according to molecular dynamics simulation, PE-plasmalogens form thicker, compressed and rigid bilayers when compared to PE-diacyl

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• in the cell membrane. Keywords: dipeptidyl peptidase enzyme; excimer; molecular dynamics simulations; phenanthridine; polynucleotide; pyrene; Introduction The design of small molecules that can selectively bind and discriminate different biomolecular structures (polynucleotides vs proteins, DNA or

• 48% for Phen-Py-1 and Phen-Py-2, respectively). The phenanthridine nitrogen was protonated under weakly acidic conditions, which made the phenanthridinium moiety relatively electron deficient compared to the electron-rich pyrene moiety that favored intramolecular stacking. Molecular dynamics

• dielectric constant and a lower polarity that influenced intramolecular stacking. To the best of our knowledge, this is the first reported phenanthridine–pyrene excimer in solution. Molecular dynamics calculations (see chapter Computational analysis) and hypochromism observed from UV–vis spectra pointed

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• [21][24][36], and recent reports show that molecular dynamics methods can eliminate the need for empirical corrections [29][30][38]. However, these calculation-intensive methods are not likely to become routine soon, potentially leaving room for empirical scaling to be useful for some time. The

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups

• Neda Rafieiolhosseini,
• Matthias Killa,
• Thorben Neumann,
• Niklas Tötsch,
• Jean-Noël Grad,
• Alexander Höing,
• Thies Dirksmeyer,
• Jochen Niemeyer,
• Christian Ottmann,
• Shirley K. Knauer,
• Michael Giese,
• Jens Voskuhl and
• Daniel Hoffmann

Beilstein J. Org. Chem. 2022, 18, 1322–1331, doi:10.3762/bjoc.18.137

• functional protein–protein binding. One theoretical option to identify putative binding sites of compound 1 on 14-3-3ζ would be by all-atom molecular dynamics (MD) simulations. However, as numerous studies have shown [21][22][23], the resources needed for a suitable sampling of such flexible systems by MD

• distribution; this approach captures ion-size effects and yields energy grids that are directly comparable to molecular dynamics simulation data. Accordingly, the 14-3-3ζ environment was scanned with the GCP and lysine ligands separately in Epitopsy using 150 rotations and a grid resolution of 0.4 Å to

• 1.5.2 [41]. To validate our method, we applied it to the QQJ-096/14-3-3/c-Raf complex for which the potential binding site was available from all-atom molecular dynamics simulations in a previous study [26]. Our results for this system are reported in the first part of the Supporting Information File 1

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• . Rather, an equilibrium may exist between GGDP and LGDP. Experimental Dynamics and Monte Carlo simulations We generated conformers using simulated annealing (SA) molecular dynamics followed by SA Monte Carlo simulation using CHARMM [28]. Force field parameters were generated using CGenFF [29] and an in

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• molecular dynamics analyses, as well as DFT calculations of the FtmOx1 reaction, suggested a modified mechanism [72][73][74]. In this mechanism, the tyrosyl radical at Tyr224 is generated by the Fe(IV)=O species, which abstracts a hydrogen atom at C21 to form an endoperoxide ring through the reaction with

• -configuration. These biochemical and biophysical analyses of NvfI suggested that NvfI catalyzes the endoperoxide formation reaction through a different mechanism from those of COX and FtmOx1. Further computational studies and mechanistical studies are now in progress in our laboratories to clarify the molecular

• dynamics of the active site during the enzyme reaction. Conclusion Endoperoxide compounds have recently attracted keen attention as a source of new drug leads, due to their unique structures and remarkable biological activities. To date, the total synthesis of endoperoxide-containing natural products and

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• its native binding partner β-catenin. An increased proteolytic stability against proteinase K has been demonstrated. Keywords: accelerated molecular dynamics; halotryptophan; intrinsically disordered peptides; late-stage diversification; macrocyclisation; molecular dynamics; stapled peptides; Suzuki

• cyclised RGD peptides. It could be proven that an isomerisation is not caused by the cross-coupling but by the presence of stable isomers/conformers. Molecular dynamics (MD) simulations verified the appearance of stable, distinct conformers or atropisomers, which were in accordance with the experimental

• . The conformational preferences of the stapled peptide P5 and of the linear peptides P6 and aAxWt were investigated via extensive accelerated molecular dynamics simulations (aMD) as implemented within the Amber18 program package [85]. The aMD methodology developed by McCammon and co-workers [86] has

GlycoBioinformatics

• Kiyoko F. Aoki-Kinoshita,
• Frédérique Lisacek,
• Niclas Karlsson,
• Daniel Kolarich and
• Nicolle H. Packer

Beilstein J. Org. Chem. 2021, 17, 2726–2728, doi:10.3762/bjoc.17.184

• article by Barnett et al. [2] uses molecular dynamics to show that O-linked glycosylation alters peptide conformation, which influences the binding of the peptides to antibodies, despite the fact that glycans are not directly involved in the binding. Another molecular modeling article by Fogarty et al. [3

• one of the authors of this article, Fadda, used glyco-adapted molecular dynamics to explain in a separate publication [4] how the COVID-19 spike protein recognition element requires N-linked glycosylation to be exposed. Another approach to understanding glyco-interactions is described in a review

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• docking results were edited using the Visual Molecular Dynamics 1.9.3 (VMD) program (available for download at http://www.ks.uiuc.edu/Research/vmd/vmd-1.9.3/). Proposed structural modifications to obtain triazole derivatives 1a, b and 2a–j. Asymmetric unit representation of the 1,2,3-triazole derivative

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• . The analysis of the melting temperature of the duplex and extensive molecular dynamics studies revealed that the synthesized double-headed nucleotides behave as functional dinucleotide mimics and hybridize with complementary targets neatly with their Watson–Crick faces compatible with natural DNA [39

• that resulted in the formation of two novel nucleic acid motifs. The novel nucleic acid motifs could be incorporated either single or multiple times in dsDNA duplexes without altering its stability. It was revealed by molecular dynamics (MD) simulations that the DNA sugar–phosphate backbone

• strands. Oligonucleotides with fourteen consecutive incorporations of different double-headed nucleosides were synthesized and the DNA duplexes showed increased stability owing to increased stacking interactions among the nucleobases of the opposite strands [72]. Molecular dynamics simulations

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• distance restraints for ion channels and other protein complexes that would be difficult to be defined by using other analytical tools. DNA and RNA secondary and tertiary structure 19F NMR spectroscopy also represents a useful analytical approach to study the structure, function and molecular dynamics of

Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• approach by investigating the in-silico binding of a peptide and glycopeptide epitope of the glycoprotein Mucin 1 (MUC1) binding with the antibody AR20.5. To study the binding, we performed molecular dynamics simulations using OpenMM and then used the Galaxy platform for data analysis. The same analysis

• . and others [14][16] provides a foundation for further investigation into the binding of glycopeptide antigens to antibodies using computational modeling. Molecular dynamics (MD) simulations and analysis thereof are a well-known ingredient of the in-silico process for mechanistic screening of

• of the analyses was carried out using Galaxy, the popular open web-based platform for bioinformatics and computational data analysis, which enables the creation of repeatable analysis pipelines (workflows). There are several well-known molecular dynamics analysis packages (MDAnalysis [37], Bio3D [38

Leveraging glycomics data in glycoprotein 3D structure validation with Privateer

• Haroldas Bagdonas,
• Daniel Ungar and
• Jon Agirre

Beilstein J. Org. Chem. 2020, 16, 2523–2533, doi:10.3762/bjoc.16.204

• study of these glycan-mediated interactions can provide unique insight into the molecular interplay governing these processes. In addition, it can provide structural snapshots in atomistic detail that can be used to generate molecular dynamics simulations describing a wider picture underpinning glycan

• /glycoproteomics to carbohydrate 3D model building and validation in Privateer Many fields, for example pharmaceutical design and engineering [58], molecular dynamics simulations [59] and protein interaction studies [60], rely upon structural biology to produce accurate atomistic descriptions of glycoproteins

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• , 3D representation of structures is provided by tools such as Visual Molecular Dynamics (VMD) [21] , and LiteMol [22], which allow for quick analysis of structural features in 3D space. All the tools mentioned were evaluated against a set of pre-selected criteria relating to ease of use, scientific

• models. These tools generally use 3D molecular templates of monosaccharides to reconstruct a 3D model. Energy minimisation methods can further refine the models. These models are essential for structure-based studies and complex calculations like Molecular Dynamics simulations. Therefore, the accurate

• incorporating SNFG symbols in 3D space for further visualisation using the computational tools like visual molecular dynamics (VMD) [21] LiteMol [22] and Sweet Unity Mol [32]. Glycan sketchers SugarSketcher. SugarSketcher [14] is a JavaScript interface module currently included in the tool collection of

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• undetected because of their intrinsic structural disorder. In this work we use molecular dynamics (MD) simulations to provide insight into N-glycans’ 3D structure by analysing the effects of a set of very specific modifications found in plants and invertebrate N-glycans, which are immunogenic in humans. We

• relationships in complex carbohydrates, with important implications in glycoengineering design. Keywords: complex carbohydrates; fucose; glycoblocks; molecular dynamics; molecular recognition; N-glycans; xylose; Introduction Complex carbohydrates (or glycans) are an essential class of biomolecules, directly

• glycans sequence can alter their 3D structure and conformational dynamics, ultimately regulating recognition [19]. In this work we use molecular dynamics (MD) simulations to analyse the effects of the inclusion of motifs typically found in plants and invertebrates N-glycans and immunogenic in mammals [20

pH- and concentration-dependent supramolecular self-assembly of a naturally occurring octapeptide

• Goutam Ghosh and
• Gustavo Fernández

Beilstein J. Org. Chem. 2020, 16, 2017–2025, doi:10.3762/bjoc.16.168

• (Glu−) amino acids [73][74]. Mechanistic insights into the observed conformational transformation via molecular dynamics simulations are underway in our laboratory. Conclusion In summary, we synthesized a naturally occurring amphiphilic peptide fragment, PEP-1, from a β-sheet lectin protein, galectin-1

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• mechanism studies using computational chemistry methods. The probable reaction mechanisms were studied by hybrid DFT QM/MM molecular dynamics simulations [11] where the possible transition state (TS) structures were localized. The observation of the possible TS structure opens the opportunities for the in

• structures. All fructofuranose and tagatofuranose derivatives were docked into the GlfT2 structure obtained by QM/MM molecular dynamics simulations, which representes the structure close to the transition state structure of the GlfT2 catalytic reaction. The best ten docking poses of each docked molecule were

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• become apparent [40]. This is because non-equilibrium structures such as transition states that cannot be described by the conventional Lewis model are passed through during reactions. Quantum chemical methods, often in combination with molecular dynamics, can predict the course of a specific reaction

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• stereoselective approaches of substrates and reagents or catalysts in a variety of processes. Examples include the substrate–enzyme recognition (the host–guest interaction) responsible for inducing pharmacological activity, the DNA-intercalation capable of generating biomolecular activity, molecular dynamics [63

Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment

• Jan Geldsetzer and
• Markus Kalesse

Beilstein J. Org. Chem. 2020, 16, 670–673, doi:10.3762/bjoc.16.64

• of the molecule was elucidated by a combination of NMR, UV and IR spectroscopy and molecular dynamics calculations (MD, MM2) [12]. However, its (Z)-enamide motif and the polyoxygenated middle segment are synthetically challenging. Results and Discussion Synthesis of amide 3 Here we report our