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

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

• carried out, reaching higher molecular weights and yields compared to catalysis with the micelle-forming refolding reagent PE–PEG. Minimum of MPD molecules was analyzed by molecular dynamics studies to enable refolding of SDS-denatured transmembrane protein FhuA ΔCVFtev [29]. This report aims to

•  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

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• aminomonosaccharides 9 and 13 are interesting moieties, regarding their resemblance with the bioactive (+)-muscarine 14 (Figure 2). Indeed, ongoing docking and molecular dynamics experiments revealed the amino-AnGal moiety as a promising platform to launch the design of new mAChR modulators [11]. The differences in

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

• ; molecular dynamics; Introduction Evolution is a unique optimization mechanism. Firstly, it stops optimizing as soon as an acceptable solution is reached. There is no evolutionary pressure for elegance, simplicity or even effectiveness above the critical threshold. Secondly, because evolution always starts

• experimental findings [29] suggest that both an agonist ligand and a bound G-protein are necessary in order to activate GPCRs. It is therefore significant that the first molecular dynamics (MD) simulations of a ternary GPCR complex were reported only four years ago [30]. Such simulations are now commonplace

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• selectivity trend was explained in terms of both adsorption mode on and relative accessibility to Pd active sites, depending on surface potentials and hindrance of modifiers, on the basis of density functional theory and molecular dynamics calculations. The rationale was summarized in the so-called

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

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

• . 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

• : 2K points acquired in the F2 domain, 512 increments and subsequent zero-filling to 1K to process data. Molecular dynamics simulations The simulations employed InsightII/Discover [15] with the CVFF force field [16]. The structure of molecules 1 and 2 were first subjected to an MD run in vacuo and

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

• 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

• , these fragments can be joined to obtain a possible new drug molecule. In the SILCS (site identification by ligand competitive saturation) method, molecular dynamics simulations are used to identify fragments that bind to a target [161][162]. SILCS uses explicit molecular dynamics simulations where the

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• [31][32][33][34]. To acquire evidence for non-statistical dynamic effects, molecular dynamics (MD) simulations are run for a statistically relevant number of trajectories (typically on the order of hundreds or thousands, depending on the system and the starting point for trajectories) [35][36]. The

• –Oppenheimer Molecular Dynamics (BOMD) calculations, so that nuclear motion and electronic structure are calculated separately, the former propagated classically and the latter determined using quantum mechanics. As with any computational (or experimental) study, there will always be a tradeoff between

• commonly used [35][36][37][38][39][40]. In particular, the B3LYP and mPW1PW91 functionals, along with small to medium sized basis sets have seen the most use in studying carbocation rearrangements of relevance to biosynthesis [6]. Using molecular dynamics trajectories to rationalize experimental results is

Aggregation behavior of amphiphilic cyclodextrins in a nonpolar solvent: evidence of large-scale structures by atomistic molecular dynamics simulations and solution studies

• Giuseppina Raffaini,
• Fabio Ganazzoli and
• Antonino Mazzaglia

Beilstein J. Org. Chem. 2016, 12, 73–80, doi:10.3762/bjoc.12.8

• have been usually investigated and characterized in water for their potential use as nanocarriers for drug delivery, but they can also aggregate in apolar solvents, as shown in the present paper through atomistic molecular dynamics simulations and dynamic light scattering measurements. The simulations

• nanoaggregates even in apolar solvents. Keywords: aggregation; amphiphilic cyclodextrins; molecular dynamics; nanoparticles; self-assembly; simulations; Introduction Amphiphilic cyclodextrins (aCD) are a class of molecules highly investigated for their self-assembly properties and inherent potential

• shown in Scheme 1b (n = 1), dissolved in an apolar solvent and an atomistic Molecular Dynamics study of a model compound (n = 0 in Scheme 1) carried out in vacuo. In particular, the latter approach aims to model the bottom-up aggregation of the model aCD molecules, an approach that was started in [11

Polydisperse methyl β-cyclodextrin–epichlorohydrin polymers: variable contact time ¹³C CP-MAS solid-state NMR characterization

• Isabelle Mallard,
• Davy Baudelet,
• Franca Castiglione,
• Monica Ferro,
• Walter Panzeri,
• Enzio Ragg and
• Andrea Mele

Beilstein J. Org. Chem. 2015, 11, 2785–2794, doi:10.3762/bjoc.11.299

• information (the chemical connectivity) and dynamic insights (the overall molecular dynamics in the solid state). Pines et al. [38] were the first to discuss the effect of different types of motion – such as molecular conformational changes, molecular reorientation and macroscopic sample rotation – on the CP

Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin

• Waratchada Sangpheak,
• Jintawee Kicuntod,
• Roswitha Schuster,
• Thanyada Rungrotmongkol,
• Peter Wolschann,
• Nawee Kungwan,
• Helmut Viernstein,
• Monika Mueller and
• Piamsook Pongsawasdi

Beilstein J. Org. Chem. 2015, 11, 2763–2773, doi:10.3762/bjoc.11.297

• hesperetin with cyclodextrins (β-CD and DM-β-CD) were theoretically investigated by molecular dynamics simulation. The free energy values obtained suggested a more stable inclusion complex with DM-β-CD. The vdW force is the main guest–host interaction when hesperetin binds with CDs. The phase solubility

• physical properties and biological activities of hesperetin and naringenin through complexation with cyclodextrins. Computational tools (molecular dynamics simulation) were adopted to first predict the stability of flavanones/CDs inclusion complexes. Consequently, the experimental phase solubility and

• values showed the same trend with values from molecular dynamics simulation that complexing with DM-β-CD was more effective than with β-CD, and the values obtained were in good agreement with the previous report [42]. These results suggested that both flavanones bind to and interact with DM-β-CD stronger

Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations

• Giuseppina Raffaini,
• Antonino Mazzaglia and
• Fabio Ganazzoli

Beilstein J. Org. Chem. 2015, 11, 2459–2473, doi:10.3762/bjoc.11.267

• report a theoretical study of the aggregation of a few amphiphilic cyclodextrins carrying hydrophobic thioalkyl groups and hydrophilic ethylene glycol moieties at opposite rims, focusing on the initial nucleation stage in an apolar solvent and in water. The study is based on atomistic molecular dynamics

• correlating their structures with the pharmaceutical properties. Keywords: aggregation; amphiphilic cyclodextrins; micelles; molecular dynamics simulations; nanoparticles; self-assembly; Introduction Inclusion complexes with supramolecular structures formed by native or modified cyclodextrins (CDs) are

• supramolecular aggregates was seldom, if ever, considered, apart from the above-mentioned reference [35]. To improve our understanding of the factors driving the formation of aCD molecular assemblies, we describe in this paper an atomistic molecular dynamics investigation of a model compound of a non-ionic aCD

Co-solvation effect on the binding mode of the α-mangostin/β-cyclodextrin inclusion complex

• Chompoonut Rungnim,
• Sarunya Phunpee,
• Manaschai Kunaseth,
• Supawadee Namuangruk,
• Kanin Rungsardthong,
• Thanyada Rungrotmongkol and
• Uracha Ruktanonchai

Beilstein J. Org. Chem. 2015, 11, 2306–2317, doi:10.3762/bjoc.11.251

• anion affinity and selectivity of a neutral anion receptor, bis(cyclopeptide) [17]. Molecular dynamics (MD) simulations can give important insights into the energetics of structural interactions. The hydrated structure of β-CD in aqueous solution [18] and those showing host–guest interactions between

• given in Table 1. Details of molecular dynamics simulations In the present study, all MD simulations were performed using the SANDER module of the Amber10 software package in accordance with the recently reported MD simulations of flavonoid/β-CD inclusion complexes in water [34][35]. The particle-mesh

A comprehensive study of olefin metathesis catalyzed by Ru-based catalysts

• Albert Poater and
• Luigi Cavallo

Beilstein J. Org. Chem. 2015, 11, 1767–1780, doi:10.3762/bjoc.11.192

• bond of C2H4 is nearly perpendicular to the Ru–methylidene bond, whereas in the bigger substrate the tether forces the coordinated C=C bond to be almost aligned with the Ru–alkylidene bond. However, the molecular dynamics simulations (vide infra) clearly indicate that in the trans geometries the C2H4

Peptide–polymer ligands for a tandem WW-domain, an adaptive multivalent protein–protein interaction: lessons on the thermodynamic fitness of flexible ligands

• Katharina Koschek,
• Vedat Durmaz,
• Oxana Krylova,
• Marek Wieczorek,
• Shilpi Gupta,
• Martin Richter,
• Alexander Bujotzek,
• Christina Fischer,
• Rainer Haag,
• Christian Freund,
• Marcus Weber and
• Jörg Rademann

Beilstein J. Org. Chem. 2015, 11, 837–847, doi:10.3762/bjoc.11.93

• precipitation. Experimental results were compared with parameters obtained from molecular dynamics simulations in order to understand the observed differences between the three carrier materials. In summary, the more rigid and condensed peptide–polymer conjugates based on the dextran scaffold seem to be

• understanding of structure–activity relationships of polymeric ligands. For this purpose, the thermodynamics and the stoichiometry of protein binding events were determined experimentally for all multivalent ligands. Finally, atomistic molecular dynamics simulations were conducted in order to rationalize the

• bivalent binding mode for the complex of Dex-2 and tandem-WW-FBP21, which is supported also by the solubility of the non-crosslinked peptide-polymer–protein complex. Molecular dynamics simulations of multivalent ligands In order to better understand our experimental observations regarding binding

Synthesis of carbohydrate-scaffolded thymine glycoconjugates to organize multivalency

• Anna K. Ciuk and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 668–674, doi:10.3762/bjoc.11.75

• [6]. This work is based on the idea that changes of ligand orientation as well as changes of their conformational availability are regulating parameters in carbohydrate recognition, in particular on the cell surface. Indeed, we have formerly shown that the molecular dynamics of glycodendrimers

Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• equilibrium of articulated rods The fundamental feature of articulated rods is the restricted conformational space with two dominating species: a stretched and a folded conformation. This feature was concluded from Molecular Dynamics (MD) simulation revealing a bimodal distribution of the end-to-end distance

Synthesis and characterization of a new photoinduced switchable β-cyclodextrin dimer

• Florian Hamon,
• Claire Blaszkiewicz,
• Marie Buchotte,
• Estelle Banaszak-Léonard,
• Hervé Bricout,
• Sébastien Tilloy,
• Eric Monflier,
• Christine Cézard,
• Laurent Bouteiller,
• Christophe Len and
• Florence Djedaini-Pilard

Beilstein J. Org. Chem. 2014, 10, 2874–2885, doi:10.3762/bjoc.10.304

• calculations, the geometrical force field parameters needed for molecular dynamics simulations were derived. Molecular dynamics simulations performed on the two configurations of AZO-CDim 1 highlighted the rigidity of the linker, which governs the relative position of the two CD cavities. The trajectories

• objects in solution. The experimental data strongly suggests that AZO-CDim 1 is a switchable host which forms two different inclusion complexes with this ditopic guest. The structural analyses of the molecular dynamics trajectories of the two configurations of the AZO-CDim 1 systems enable us to draw some

• moiety as the linker [36]. At this stage, based on the molecular dynamics study, at least two supramolecular polymers can be considered: the first is linear, as often described in the literature [43][44] (Figure 8b), and the second is cyclic (Figure 8c). Furthermore, it is possible that such linear or

Binding mode and free energy prediction of fisetin/β-cyclodextrin inclusion complexes

• Bodee Nutho,
• Wasinee Khuntawee,
• Chompoonut Rungnim,
• Piamsook Pongsawasdi,
• Peter Wolschann,
• Alfred Karpfen,
• Nawee Kungwan and
• Thanyada Rungrotmongkol

Beilstein J. Org. Chem. 2014, 10, 2789–2799, doi:10.3762/bjoc.10.296

• to investigate the preferential binding mode and encapsulation of the flavonoid fisetin in the nano-pore of β-cyclodextrin (β-CD) at the molecular level using various theoretical approaches: molecular docking, molecular dynamics (MD) simulations and binding free energy calculations. The molecular

• complexes. In addition, the quantum mechanics calculations with M06-2X/6-31G(d,p) clearly showed that both solvation effect and BSSE correction cannot be neglected for the energy determination of the chosen system. Keywords: cyclodextrin; fisetin; flavonoid; MM-PBSA; molecular dynamics simulation; QM-PBSA

• stability against exposure to strong UV light and high temperatures [24][25]. In recent years, computational approaches have played a significant role in monitoring inclusion complexation between cyclodextrin and guest molecules [26][27] at the molecular level [28][29]. Molecular dynamics (MD) simulations

Specific DNA duplex formation at an artificial lipid bilayer: fluorescence microscopy after Sybr Green I staining

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2014, 10, 2307–2321, doi:10.3762/bjoc.10.240

• values of ≈5 × 104 kHz. Further experiments concerning a multiple compartment chamber with a common aqueous sub-phase, as well as a thermostated device for a suppression of nonspecific base pairing are underway [15]. Moreover, ab initio molecular-dynamics- (AIMD)- and ab initio Monte-Carlo- (AIMC

Why a diaminopyrrolic tripodal receptor binds mannosides in acetonitrile but not in water?

• Diogo Vila-Viçosa,
• Oscar Francesconi and
• Miguel Machuqueiro

Beilstein J. Org. Chem. 2014, 10, 1513–1523, doi:10.3762/bjoc.10.156

• several molecular dynamics and constant-pH molecular dynamics simulations in acetonitrile and water to evaluate the conformational space of the receptor and to understand the molecular detail of the receptor–mannoside interaction. The protonation states sampled by the receptor show that the positive

• reason for the higher activity in this solvent. This work also presents a new implementation of the stochastic titration constant-pH molecular dynamics method to a synthetic receptor of sugars and attests its ability to describe the protonation/conformation coupling in these molecules. Keywords

• performances when changing the solvent and to identify the molecular determinants behind the reported high affinities. Simulation methods, namely the so-called constant-pH molecular dynamics (CpHMD) methods, have been used to understand the molecular detail of several phenomena in the last years [15][16][17

Biantennary oligoglycines and glyco-oligoglycines self-associating in aqueous medium

• Svetlana V. Tsygankova,
• Alexander A. Chinarev,
• Alexander B. Tuzikov,
• Nikolai Severin,
• Alexey A. Kalachev,
• Juergen P. Rabe,
• Alexandra S. Gambaryan and
• Nicolai V. Bovin

Beilstein J. Org. Chem. 2014, 10, 1372–1382, doi:10.3762/bjoc.10.140

• formation of a monolayer with the monomer conformation ”2 + 0” is favorable according to molecular dynamics simulations [13]. Minimal size of Glyn fragment providing association In the case of biantennary molecules association formally starts from the value n = 4, but, in fact, this value is supposedly

Unusual polymorphism in new bent-shaped liquid crystals based on biphenyl as a central molecular core

• Anna Kovářová,
• Svatopluk Světlík,
• Václav Kozmík,
• Jiří Svoboda,
• Vladimíra Novotná,
• Damian Pociecha,
• Ewa Gorecka and
• Natalia Podoliak

Beilstein J. Org. Chem. 2014, 10, 794–807, doi:10.3762/bjoc.10.75

• dielectric measurements. The dielectric spectroscopy data are unique and presented for the first time in the SmCG phase providing new information about the molecular dynamics. Keywords: bent-shaped; biphenyl core; liquid crystals; mesomorphic behaviour; SmCG phase; Introduction Achiral bent-shaped liquid

Cyclic phosphonium ionic liquids

• Sharon I. Lall-Ramnarine,
• Joshua A. Mukhlall,
• James F. Wishart,
• Robert R. Engel,
• Alicia R. Romeo,
• Masao Gohdo,
• Sharon Ramati,
• Marc Berman and
• Sophia N. Suarez

Beilstein J. Org. Chem. 2014, 10, 271–275, doi:10.3762/bjoc.10.22

• chains. This topic merits further exploration via molecular dynamics simulations [28] and physical studies such as NMR diffusion measurements, nuclear Overhauser effect spectroscopies, and quasi-elastic neutron scattering. As seen for instance for the cyclic ammonium salts, the viscosities of the cyclic