Correlation effects and many-body interactions in water clusters

• Andreas Heßelmann

Beilstein J. Org. Chem. 2018, 14, 979–991, doi:10.3762/bjoc.14.83

• sound models of the interaction potential for water to be used in molecular simulations. In particular, the role of many-body interactions beyond the two-body interactions, which are often not explicitly taken into account by empirical force fields, can be accurately described by quantum chemistry

• explicitly or implicitly influenced by a water environment. An example for this is the hydrogen-bond cooperativity effect that can have a significant impact on the properties of the bare solute molecules [1]. In order to describe such phenomena, computer simulations have become an indispensable tool, since

• they enable a description of water on a molecular level that often can provide further insights than are accessible from spectroscopic measurements. The basis for such simulations are the so-called force fields that describe both the covalent as well as the noncovalent interactions within the system

Crystal structure of the inclusion complex of cholesterol in β-cyclodextrin and molecular dynamics studies

• Elias Christoforides,
• Andreas Papaioannou and
• Kostas Bethanis

Beilstein J. Org. Chem. 2018, 14, 838–848, doi:10.3762/bjoc.14.69

• crystalline state comprise the asymmetric unit of the structure. The dimers are arranged in an intermediate (IM) channel packing mode in the crystal. Moreover, MD simulations, at 300 and 340 K, based on the crystallographically determined coordinates of the complex show that the formed cholesterol/β-CD

• characterization of the cholesterol/β-CD inclusion complex [22], its binding affinity [23][24][25], the inclusion mode of the complex [26] and its dynamic behavior through MD simulations [27][28][29] but its crystal structure is absent. In this work, the structure of CHL/β-CD is determined by X-ray crystallography

• and its geometrical features are examined thoroughly. In order to examine the stability of the crystallographically determined model excluding the crystal contacts observed in the crystalline state, MD simulations of the inclusion complex in aqueous environment were performed. The starting set of

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• ). Combined QM/MM simulations have lent support for this interpretation [47]. With triester analogs, such as uridine 3´-diethyl phosphate, the latter intramolecular proton transfer is not possible and the ratio kcl/kis is much smaller than with the diester analog, around 10−5 [50]. Since the barrier for the

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• dynamics simulations. CF3-threonine containing pentapeptides are more prone to mimic β-strands than their natural Ser and Thr pentapeptide analogues. The proof of concept that these fluorinated β-strand mimics are able to disrupt protein–protein interactions involving β-sheet structures is provided. The

• according to their central fluorinated or non-fluorinated residue, all-atom molecular dynamics (MD) simulations were performed using the GROMACS 4.5 package, with the OPLS-AA force field in combination with the SPC/E water model (for a complete description of the method, see Supporting Information File 1

• in order to better anticipate the peptide conformations in a solvent closer to physiological conditions. Nevertheless, we verified for compounds 2b and 4b that the simulations conducted in MeOH and in water were very similar (Figure S23, Supporting Information File 1). Overall, the theoretical 3JHN

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• well as the influence of highly mobile vs conserved waters were analyzed. For the assessment of the dynamic behavior of the ligand complexes of the seven calcium-dependent lectins, 20 ns molecular dynamics (MD) simulations were performed [57]. The most prominent interactions of O–C3 and O–C4 of the

• calcium ions. During MD simulations, the number of ligand–protein hydrogen-bond interactions for lectins A–F varied from 1.5 to 3.5, and subsequently increased to 4.5 and 5.4 for LecB (G) and BC2L-A (H), respectively. Lastly, FimH (I) forms on average 7.9 hydrogen bonds with methyl α-D-mannopyranoside (2

• close to the first calcium ion, a process which is hindered by His112 in H, leading to a 25-fold difference in affinity. However, in the case of highly mobile water molecules, water-mediated H-bonds as observed in MD simulations destabilize the carbohydrate–lectin interaction, whereas a pre-constrained

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• compounds. Model studies that informed the final steps of the synthesis. Supporting Information Supporting Information File 300: Synthetic procedures and characterisation data of intermediated, NMR spectra and NMR simulations for 6a,b. Acknowledgements L.H. thanks the Australian Research Council for

2-Methyl-2,4-pentanediol (MPD) boosts as detergent-substitute the performance of ß-barrel hybrid catalyst for phenylacetylene polymerization

• Julia Kinzel,
• Daniel F. Sauer,
• Marco Bocola,
• Marcus Arlt,
• Tayebeh Mirzaei Garakani,
• Andreas Thiel,
• Klaus Beckerle,
• Tino Polen,
• Jun Okuda and
• Ulrich Schwaneberg

Beilstein J. Org. Chem. 2017, 13, 1498–1506, doi:10.3762/bjoc.13.148

• rhodium-based biohybrid catalyst. Unlike commonly used detergents such as sodium dodecyl sulfate or polyethylene polyethyleneglycol, MPD does not form micelles in solution. Molecular dynamics simulations revealed the effect and position of stabilizing MPD molecules. The advantage of the amphiphilic MPD

•  1). Molecular dynamics (MD) simulations reveal an optimal minimum number of ≈200 MPD molecules for shielding the hydrophobic transmembrane region of FhuA ΔCVFtev MD simulations of FhuA ΔCVFtev were performed in a box with varying numbers of MPD molecules from 126 MPD, 189 MPD, 252 MPD to 378 MPD

• molecules as stabilizing cosolvent to investigate the molecular dynamics of protein structure stabilization, how a small amphiphilic molecule could stabilize a transmembrane protein such as FhuA ΔCVFtev. All simulations started with a random distribution of MPD, but after a few nanoseconds, the MPD

Grip on complexity in chemical reaction networks

• Albert S. Y. Wong and
• Wilhelm T. S. Huck

Beilstein J. Org. Chem. 2017, 13, 1486–1497, doi:10.3762/bjoc.13.147

• were determined from kinetic studies in isolated individual reactions, allowing accurate simulations to test specific details of the experiments. We used the model to vary the rate constant that is induced by the changes to the molecular structure. First we show in Figure 7b that the tuning of R1

• predator–prey network. Adapted with permission from [88], copyright 2013 American Chemical Society. (b) The gene regulation pathway and of an oscillator based on a positive and delayed negative feedback motif, with experimentally observed oscillations shown to be in good agreement with the simulations

• . Adapted with permission from [90], copyright 2011 the authors. (c) Oscillations in the dual-feedback motif. (d) Illustration of the explicit intermediate processes required for accurate simulations in the mathematical modelling of genetic reaction networks. Adapted with permission from [91], copyright

Towards open-ended evolution in self-replicating molecular systems

• Herman Duim and
• Sijbren Otto

Beilstein J. Org. Chem. 2017, 13, 1189–1203, doi:10.3762/bjoc.13.118

• uncatalyzed pathways and can therefore have a value smaller than 1, even for cases where the autocatalytic pathway itself would have a reaction order r = 1. In such situations computational simulations of the system can provide additional information on the replication processes that are involved [29]. 2.4

Kinetic analysis of mechanoradical formation during the mechanolysis of dextran and glycogen

• Naoki Doi,
• Yasushi Sasai,
• Yukinori Yamauchi,
• Tetsuo Adachi,
• Masayuki Kuzuya and
• Shin-ichi Kondo

Beilstein J. Org. Chem. 2017, 13, 1174–1183, doi:10.3762/bjoc.13.116

• on ESR spectra coupled with systematic computer simulations, in comparison with the mechanolysis of amylose. The component spectra of Dx and Gly were essentially identical to those of amylose and remained nearly unchanged in the course of vibratory milling. Simulated Dx, Gly, and amylose spectra were

• also obtained from admixtures of the component spectra at different ratios. Computer simulations revealed that a singlet spectrum (II) assignable to the immobilized DBS was a major component of milled Dx and Gly. The generated Dx and Gly mechanoradicals dissipated more readily than amylose

• particle diameter were determined by the histogram method with the Marquardt calculation. Computer simulations of ESR spectra Analogous to the description in [5], computational simulations were performed on a personal computer (DELL Inspiron 545S) using a simulation program developed in our laboratory. The

Correlation of surface pressure and hue of planarizable push–pull chromophores at the air/water interface

• Frederik Neuhaus,
• Fabio Zobi,
• Gerald Brezesinski,
• Marta Dal Molin,
• Stefan Matile and
• Andreas Zumbuehl

Beilstein J. Org. Chem. 2017, 13, 1099–1105, doi:10.3762/bjoc.13.109

• . Computational simulations Geometry optimization, as well as frequency calculations for the flipper mechanophore, were performed in the gas phase at the density functional level of theory with the Gaussian 03 program package [35] using the hybrid B3LYP functional [36] in conjunction with the LanL2DZ basis set

G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• Timothy Clark Computer-Chemie-Centrum, Department of Chemistry and Pharmacy, Friedrich-Alexander-University Erlangen-Nuernberg, Naegelsbachstr. 25, 91052 Erlangen, Germany 10.3762/bjoc.13.106 Abstract Molecular-dynamics (MD) simulations are playing an increasingly important role in research into

• the modes of action of G-protein coupled receptors (GPCRs). In this field, MD simulations are unusually important as, because of the difficult experimental situation, they often offer the only opportunity to determine structural and mechanistic features in atomistic detail. Modern combinations of soft

• - and hardware have made MD simulations a powerful tool in GPCR research. This is important because GPCRs are targeted by approximately half of the drugs on the market, so that computer-aided drug design plays a major role in GPCR research. Keywords: computer-aided drug design; GPCR; metadynamicxs

Cycloheximide congeners produced by Streptomyces sp. SC0581 and photoinduced interconversion between (E)- and (Z)-2,3-dehydroanhydrocycloheximides

• Li Yang,
• Ping Wu,
• Jinghua Xue,
• Huitong Tan,
• Zheng Zhang and
• Xiaoyi Wei

Beilstein J. Org. Chem. 2017, 13, 1039–1049, doi:10.3762/bjoc.13.103

• new compounds were achieved by spectroscopic analysis in combination with theoretical conformational analysis and ECD simulations, in which theoretical computations were shown to play a key role in solving challenges in assignments of relative and absolute configurations. Analysis of the antifungal

Aggregation behaviour of a single-chain, phenylene-modified bolalipid and its miscibility with classical phospholipids

• Simon Drescher,
• Vasil M. Garamus,
• Christopher J. Garvey,
• Annette Meister and
• Alfred Blume

Beilstein J. Org. Chem. 2017, 13, 995–1007, doi:10.3762/bjoc.13.99

• simulations [27]. A temperature increase leads to a transformation of the nanofibres into small micelles and the gel character is lost. This reversible gel/sol transformation is accompanied by a cooperative endothermic transition at Tm = 48 °C, which can be followed by differential scanning calorimetry (DSC

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• (viz. forcefully quenching the reaction). There should also be a sequence of operation procedures which can take the process from one state of operating conditions to another state of operation. Dynamic simulations can be a useful tool to study the special purpose operations (viz. start-up, shut-down

Membrane properties of hydroxycholesterols related to the brain cholesterol metabolism

• Malte Hilsch,
• Ivan Haralampiev,
• Peter Müller,
• Daniel Huster and
• Holger A. Scheidt

Beilstein J. Org. Chem. 2017, 13, 720–727, doi:10.3762/bjoc.13.71

• fluorescence techniques [21]. Also, a decreased but still significant effect of the hydroxysterols on lipid condensation compared to native cholesterol was found in molecular dynamics simulations, which is probably caused by an increased tilt angle of the sterols to the membrane normal [8][21]. However, using

• estradiol was found in the lipid water interface of the membrane with an orientation perpendicular to the membrane normal. By that, the molecules act disturbing rather than ordering. Notably, MD simulations found an opposite effect of the hydroxycholesterols [21]. The additional polarity of

• proteins) is impacted. MD simulations for 27-HC have shown, that this molecule adopts compared to cholesterol different orientations within the membrane, which are upside-down, largely tilted and/or inter-leaflet positions [21]. These properties indicate that the molecules are less strongly anchored within

Inclusion complexes of β-cyclodextrin with tricyclic drugs: an X-ray diffraction, NMR and molecular dynamics study

• Franca Castiglione,
• Fabio Ganazzoli,
• Luciana Malpezzi,
• Andrea Mele,
• Walter Panzeri and
• Giuseppina Raffaini

Beilstein J. Org. Chem. 2017, 13, 714–719, doi:10.3762/bjoc.13.70

• /β-CD and 2/β-CD complexes, with the aromatic ring system entering the cavity from the large rim of the cyclodextrin and the alkylammonium chain protruding out of the cavity and facing the secondary OH rim. These features matched those found in the molecular dynamics (MD) simulations in solution and

• in the solid state from single-crystal X-ray diffraction of 1/β-CD and 2/β-CD complexes. The latter complex was found in a single conformation in the solid state, whilst the MD simulations in explicit water reproduced the conformational transitions observed experimentally for the free molecule

• . Keywords: amitriptyline; β-cyclodextrin; crystal structure; cyclobenzaprine; molecular dynamics simulations; NOE; Introduction The present paper reports on a multidisciplinary approach [1][2] based on single crystal X-ray diffraction, solution NMR spectroscopy and molecular dynamics (MD) simulations with

Conjecture and hypothesis: The importance of reality checks

• David Deamer

Beilstein J. Org. Chem. 2017, 13, 620–624, doi:10.3762/bjoc.13.60

• within a two dimensional plane with the result that polymerization is enhanced [24][25]. The hydrothermal field hypothesis has been tested in laboratory simulations. For instance, peptide bonds have been produced [26][27] and cycles of drying and rehydration have been shown to drive polymerization of

• condition in the above list can be tested by observation, by theoretical analysis or in laboratory simulations. If any one of the predictions fails experimentally or is shown to be impossible, for instance by being inconsistent with thermodynamic principles, that alternative can be considered to be

• falsified. As evidence accumulates, we will be able to judge the relative plausibility and explanatory power of the competing ideas. Continued testing of the alternative hypotheses is essential, because neither has yet reached the level of consensus. In both cases, laboratory simulations will ideally be

Synthesis and optical properties of new 5'-aryl-substituted 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazoles

• Anastasia S. Kostyuchenko,
• Tatyana Yu. Zheleznova,
• Anton J. Stasyuk,
• Aleksandra Kurowska,
• Wojciech Domagala,
• Adam Pron and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2017, 13, 313–322, doi:10.3762/bjoc.13.34

• and aromatic conjugation. Initially, for optical transition simulations, we have used the same functional and basis set as has been used for the ground state geometry optimization, i.e., B3LYP/Def2-SVPD/IEFPCM(DCM). However, the obtained excitation energies revealed an extremely poor agreement between

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• den Berg et al. [23] and obtained from finite-element simulations [24]. High SNR were obtained at a low-field magnet. Another disadvantage of planar coils is the weak and inhomogenous B1-field produced by the coil resulting in a non-sinusoidal nutation curve and in low SNR of the free induction decay

Self-optimisation and model-based design of experiments for developing a C–H activation flow process

• Alexander Echtermeyer,
• Yehia Amar,
• Jacek Zakrzewski and
• Alexei Lapkin

Beilstein J. Org. Chem. 2017, 13, 150–163, doi:10.3762/bjoc.13.18

• model. The latter is frequently used in expensive computer experiments, and in the case of large-scale process simulations, when evaluations of process models is computationally too expensive. In the case of our test reaction the MBDoE approach enabled us to develop a reasonably good process model in a

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• , agonists, inhibitors, etc. of a target) design. Molecular dynamics (MD) simulations are frequently used in SBDD to give insights into not only how ligands bind with target proteins but also the pathways of interaction and to account for target flexibility. This is especially important when drug targets are

• the Zhang group has also shown great success in recent CASP experiments [57]. QUARK uses atomic knowledge-based potential functions and models are built from small residue fragments by replica exchange Monte Carlo simulations. In both CASP9 and CASP10, QUARK was the number one ranked server in the

• AMBER [120] (Assisted Model Building and Energy Refinement) which have been built mainly for molecular dynamics simulations. The molecular docking program DOCK [121] uses force-field based scoring functions derived from molecular dynamics force-field AMBER. Empirical scoring functions Empirical scoring

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• ]. In the same idea, Mascetti et al. proposed that CDs interact directly with cholesterol [82]. Based on molecular simulations, López et al. proposed the following mechanism: i) association of CDs in aqueous solution to form dimers, ii) binding of dimers at the membrane surface, iii) extraction and