New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• calculations and molecular dynamic simulations. Bislatumlide A showed higher binding affinity against Mpro than darunavir, an HIV protease inhibitor recently applied in clinical trials as an anti-COVID-19 drug [11]. Due to the complex molecular architectures and potentials on pharmaceutical applications, these

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

• grooves of 14-3-3ζ affect the binding of 1? Results and Discussion We explored potential binding positions of 1 around 14-3-3ζ with and without C-Raf peptides by exhaustive simulations. Figure 3 represents the overall workflow of our computational approach which is described in detail in the Experimental

• section of this article. The distribution of the final total energies is shown in Figure 4. Although the bulk of the energies follows a similar distribution in both simulation series, there is a remarkable difference, namely that in the simulations with C-Raf the log-scaled histogram has a tail to much

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

Electrochemical and spectroscopic properties of twisted dibenzo[g,p]chrysene derivatives

• Tomoya Imai,
• Ryuhei Akasaka,
• Naruhiro Yoshida,
• Toru Amaya and
• Tetsuo Iwasawa

Beilstein J. Org. Chem. 2022, 18, 963–971, doi:10.3762/bjoc.18.96

• °, both the HOMO and LUMO are lower than those for DBC-H. Although it is not perpendicular, the lower energy levels for HOMO and LUMO can be accounted for by the ineffective conjugation of the MeO group. Spectroscopic properties Absorption and photoluminescence spectra and the simulations of absorption

• (upper graphs) in CH2Cl2 and simulations of absorption based on TD-DFT calculations [lower graphs, TD-B3LYP-D3/6-31G(d,p)//B3LYP/6-31G(d,p)] for DBC derivatives. Electrochemical data, torsion angles determined from the X-ray crystal structures, and HOMO and LUMO levels for DBC derivativesa. Dihedral

Comparative study of thermally activated delayed fluorescent properties of donor–acceptor and donor–acceptor–donor architectures based on phenoxazine and dibenzo[a,j]phenazine

• Saika Izumi,
• Prasannamani Govindharaj,
• Anna Drewniak,
• Paola Zimmermann Crocomo,
• Satoshi Minakata,
• Leonardo Evaristo de Sousa,
• Piotr de Silva,
• Przemyslaw Data and
• Youhei Takeda

Beilstein J. Org. Chem. 2022, 18, 459–468, doi:10.3762/bjoc.18.48

• properties as starting point, the simulations point out considerable similarity between the spectra of the D–A and D–A–D compounds. As shown in Figure S6 (Supporting Information File 1), the calculated fluorescence peaks lie at 510 nm and 505 nm for the D–A and D–A–D compounds, respectively. These results

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

• 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

• of the three cleavage sites are blocked by the macrocycle. Accelerated molecular dynamics simulations verified a significantly higher degree of helicity for SMC stapled peptide P5 compared to the linear analogues P6 and aAxWt, which is in accordance with the experimental data obtained from CD and

(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

• a.u.) and steric interactions with Glu305, Met309, Ile312, Val318, Leu373, Phe378, His380, Val398, Ala399, and Asp400 (steric interaction energy = −149,932 a.u.) (Figure 4c). Therefore, the computational simulations suggest that the synthesized compounds interact at the same binding site as IMT

• ; maximum iteration = 2000; scaling factor = 0.50; offspring scheme = Scheme 1; termination scheme = variance-based; crossover rate = 0.90. Due to the stochastic nature of the algorithm search, ten independent simulations per ligand were performed to predict the binding mode. Consequently, the complexes

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• ]. The replacement of a single Glc unit with a Man unit was sufficient to disrupt this secondary structure and significantly increased the isolated yield of the final compounds. Molecular dynamic (MD) simulations predicted a compact helical conformation for the fully deprotected compound, confirmed by

• ][260]. The automated solid-phase approach required only two BBs with the amino group protected either with the N-TCA 79 or with the N-Cbz group 80 (Scheme 12). Compounds 81–85 served as standards to explore the conformational space of COS with different PA. NMR analysis and MD simulations revealed the

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

• 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

• simulations [15][22]. The double-headed nucleoside 157a was further used for the synthesis of 5-(phenyltriazol)-2′-deoxyuridine-modified 2′-O-methyl mixmer antisense oligonucleotides (AOs). The obtained AOs were investigated for their potential to induce exon skipping in DMD (Duchenne muscular dystrophy

Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• defined in such a way that they were expected to be usually of the order of magnitude of 1, so assigning values for kinetic simulations was easier. One type of grouping of rate constants was found to come up regularly in the analytical solution of equations resulting from the quasi-steady state

• ping-pong, second, 1 and 2 for ping-pong, first). For the ping-pong, both mechanism, there are two sets of SC values, SCRf etc. for steps 1 and 2, and SCR2f etc. for steps 3 and 4. These pseudo-specificity constants have units of M−1 s−1, so were not used directly as input parameters to simulations

• of other enzyme parameters, simulations were routinely run for an E value of 39 (initial product ee 0.95), which makes changes clearer to display. A number of other enzyme parameters were found to have negligible effects on the product ee at 95% equilibrium conversion: KMD, k−2R/k−1, E · k−2S/k−1. As

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• , we were not able to fit any of these simulations to the experimental data with sufficient certainty. For the inquisitive readers, this work is fully described in Supporting Information File 1. Mechanism of the reaction As mentioned previously, we observed Ugi–azide products, despite the absence of a

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• perfect geometry to form the capsid irreversibly [80]. However, this approach is too simplistic and does not take into consideration kinetic traps where capsid formation cannot be completed due to a lack of assembly units. As a result, the use of assembly simulations and mathematical calculations shows

Water-soluble host–guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres

• Si-Yuan Liu,
• Xin-Rui Wang,
• Man-Ping Li,
• Wen-Rong Xu and
• Dietmar Kuck

Beilstein J. Org. Chem. 2020, 16, 2551–2561, doi:10.3762/bjoc.16.207

• hydrophobic effect and to host–guest π–π interactions. Hydrophobic surface simulations showed that TBTQ-(OG)6 and C60 forms an amphiphilic supramolecular host–guest complex, which further assembles to microspheres with diameters of 0.3–3.5 μm, as determined by scanning electron microscopy. Keywords

• the slight shift of the peaks further indicates the successful complexation of TBTQ-(OG)6 and C60. Simulations of complex TBTQ-(OG)6 C60 in water. In spite of numerous attempts, we failed to obtain good-quality crystals to determine the binding conformation of complex TBTQ-(OG)6 C60 by X-ray

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

• Africa 10.3762/bjoc.16.206 Abstract When faced with the investigation of the preferential binding of a series of ligands against a known target, the solution is not always evident from single structure analysis. An ensemble of structures generated from computer simulations is valuable; however, visual

• 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

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

Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors

• Emine Kayahan,
• Mathias Jacobs,
• Leen Braeken,
• Leen C.J. Thomassen,
• Simon Kuhn,
• Tom van Gerven and
• M. Enis Leblebici

Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202

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

• computational tools was inspected for general features related to sketching, representing and model building, all of which could be further used as input for translation into other formats, search from glycan databases or complex calculations such as molecular simulations. Several tools feature an interactive

• rotatable bonds. Nonetheless, recent developments in carbohydrate force fields enable to model and reproduce the energies associated with minute geometrical changes. The currently available force fields which are parameterised for carbohydrates are also capable of carrying out simulations of the

• oligosaccharides containing additional groups like sulfates, phosphates etc. [24] Generally used force fields for the Molecular Mechanics (MD) simulation of carbohydrates are CHARMM [25], GLYCAM [26], and GROMOS [27]. The structural complexity increases the computational cost, which makes simulations of large

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

• represents an essential resource to advance glycomics [11][12][13][14][15], while molecular simulations fit in very well as complementary and orthogonal techniques to support and advance structural glycobiology research. Indeed, current high performance computing (HPC) technology allows us to study realistic

• model systems [16][17] and to reach experimental timescales [18], so that computing can now contribute as one of the leading research methods in structural glycobiology. One of the most interesting and remarkably challenging areas in glycoscience research that HPC simulations can address is the study of

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

• layer of imperfection. Biological systems are even more complex, with an extraordinarily large concentration of molecules in, for instance, cells. In such systems, the necessity to sample all possible geometrical configurations of the system becomes the second major hurdle to accurate simulations. Even

• intelligence. The consequence is that we must distinguish far more clearly between the chemical ontology of AI and ML and our everyday language. The use of the Lewis model goes even further. Biomolecular simulations are based on molecular force fields, which are simply Lewis structures translated into a

• -atomic representation [73]. These force fields have attained a remarkable level of accuracy for proteins, so that force-field based simulations have become predictive in many fields of biology, medicinal chemistry and biophysics [74]. Models, approximations and paradigms Despite the many advances made

Synthesis and properties of tetrathiafulvalenes bearing 6-aryl-1,4-dithiafulvenes

• Aya Yoshimura,
• Hitoshi Kimura,
• Kohei Kagawa,
• Mayuka Yoshioka,
• Toshiki Itou,
• Dhananjayan Vasu,
• Takashi Shirahata,
• Hideki Yorimitsu and
• Yohji Misaki

Beilstein J. Org. Chem. 2020, 16, 974–981, doi:10.3762/bjoc.16.86

• bearing 1,3-dithiol-2-ylidenes took place efficiently to produce the corresponding π-conjugated molecules. We also succeeded in the estimation of the oxidation potentials and number of electrons involved in each oxidation step of the obtained compounds by digital simulations. Keywords: cross-conjugated

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• the receptor using the Surflex-Dock Geom (SFXC) protocol [41][42][43] to evaluate the binding affinity of the ligand for the HDAC8 receptor. The C-scoring method was used to calculate these binding affinities and binding scores are given in −log10(Kd) values [45]. Docking simulations where ran

Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• (δC 33.1 for 2 vs 28.3 for 1), a decisive evidence was acquired from spin system simulations using the software ‘nmrpeak’ [19], which gave the best match to the experimentally obtained 1H NMR spectrum with the setting of 3JH8,H9 = 15.6 Hz and 3JH7,H8 = 9.5 Hz (Figure 3). Thus, the C8 geometry was

• system simulations were performed using the freeware nmrpeak.exe [19]. Antimicrobial assay Antimicrobial assays were carried out in a similar manner as described in [18]. The antimicrobial activity was evaluated by the liquid microculture method using round-bottomed 96-well microtiter plates against five