Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• . CHARMM [62]: CHARMM, acronym of "Chemistry at HARvard Molecular Mechanics", is a free extensively utilised molecular modelling and simulation software package. Its force field is at the core of CHARMM's capabilities, which serves as a comprehensive set of parameters and mathematical functions to describe

• disaccharide, an exhaustive search was performed using the MM3 molecular mechanics force field [66], giving a complete sampling of the conformational space and yielding the construction of relaxed adiabatic energy maps (https://glyco3d.cermav.cnrs.fr/disac3db/). It is worth to note that the presence of

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• produce 20 random conformers from a SMILES string and optimize the structure with molecular mechanics force fields [38] using RDKit [16]. The CM5 atomic charges of the lowest-energy conformer are then used to generate atomic descriptors based on sorting the CM5 charges for a given atom of the input SMILES

Diameter-selective extraction of single-walled carbon nanotubes by interlocking with Cu-tethered square nanobrackets

• Guoqing Cheng and
• Naoki Komatsu

Beilstein J. Org. Chem. 2024, 20, 1298–1307, doi:10.3762/bjoc.20.113

• square in its shape by changing anthracene in 1a to pyrene in 1b. To interpret the results of the diameter selectivity, the theoretical calculation using the semiempirical tight binding quantum chemical method GFN2-xTB was employed instead of the molecular mechanics used in our previous works, because it

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

• analysis of the contacts between protein and GAG molecules established in the course of the simulation. Binding free energy calculations MM/GBSA (molecular mechanics generalized born surface area) model igb = 2 [48] from AMBER20 was used for free energy calculations on the trajectories obtained from RS

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• -mannosidase II (LManII) and JBMan). Finally, structural and physicochemical properties of inhibitor:enzyme complexes were investigated at the theoretical level using molecular docking, hybrid quantum mechanics/molecular mechanics (QM/MM) calculations and fragmented molecular orbital pair interaction energy

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• main product [36]. Based on molecular mechanics calculations, four conformers 1a–d have been described for 1 (Scheme 3B) [37]. The calculations revealed all four conformers are of similar stability, with 1a being the most stable conformer. The fact that 1 shows a defined set of fifteen sharp signals in

• ), B) the four conformers of 1 established by molecular mechanics calculations (energies in black boxes are relative to 1a for which the energy was set to 0.00 kcal/mol), C) Cope rearrangement to 5 and formation from 6 by pyrolysis, D) dehydration of 7 to 5 and 8. The chemistry of germacrene B (1). A

Continuous flow synthesis of azobenzenes via Baeyer–Mills reaction

• Jan H. Griwatz,
• Anne Kunz and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2022, 18, 781–787, doi:10.3762/bjoc.18.78

• and photopharmacology [7], host–guest chemistry [8], molecular mechanics [9][10], to molecular machines [11]. This popularity is due to the ability of ABs to isomerize from their energetically more stable (E)- to the meta-stable (Z)-isomer by irradiation with light [12]. During this isomerization, not

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

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

• 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

• increasing complexity. The model can be further minimised using MM2 [59] and MM3 [60] methods. The 3D models can be viewed using molecular viewers like JMol, WebMol-applet, Chemis3D-applet, etc. Besides, the program also generates additional files which can be used for molecular mechanics and molecular

• . The monosaccharides have been subjected to geometry optimisation using molecular mechanics approach. For a given input sequence, the corresponding 3D coordinates are generated at the PDB format. Within the process of construction, the structure is displayed via the LiteMol and eventually optimised to

Synthesis and properties of quinazoline-based versatile exciplex-forming compounds

• Rasa Keruckiene,
• Simona Vekteryte,
• Ervinas Urbonas,
• Matas Guzauskas,
• Eigirdas Skuodis,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101

• with the Gaussian software [26]. Firstly, the equilibrium conformer search at the ground state was performed by using the MMFF (molecular mechanics force fields) method, and this geometry was used for further optimization. The vertical singlet and triplet energy values were calculated by using the

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• inertia analysis was carried out by calculation of the lowest energy conformation of compounds 3–39 and block buster drugs. The conformation calculation was performed using the built-in AMMP molecular mechanics algorithm with default parameters of the VEGA ZZ molecular modelling software package v.3.0.1

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• provide important information to derive a synthetic strategy for cyclooctatin and related terpene manufacturing. Future studies using hybrid quantum mechanics and molecular mechanics techniques to model the enzyme reaction in a complete enzyme environment will allow careful evaluation of the usefulness of

Effect of ring size on photoisomerization properties of stiff stilbene macrocycles

• Sandra Olsson,
• Óscar Benito Pérez,
• Magnus Blom and
• Adolf Gogoll

Beilstein J. Org. Chem. 2019, 15, 2408–2418, doi:10.3762/bjoc.15.233

• the resulting macrocycle. Keywords: DFT; molecular mechanics; photostability; photo-switch; ring-strain; stiff stilbene; Introduction The stiff stilbene (SS) molecule has drawn a lot of interest due to its photodynamic properties [1]. Stiff stilbenes typically undergo light triggered isomerization

Multiple threading of a triple-calix[6]arene host

• Veronica Iuliano,
• Roberta Ciao,
• Emanuele Vignola,
• Carmen Talotta,
• Patrizia Iannece,
• Margherita De Rosa,
• Annunziata Soriente,
• Carmine Gaeta and
• Placido Neri

Beilstein J. Org. Chem. 2019, 15, 2092–2104, doi:10.3762/bjoc.15.207

• . This result was also confirmed by the minimum-energy structure of (7+)36 obtained by molecular mechanics calculations (Figure 6), which evidenced the typical stabilizing H-bonding interactions between the ammonium groups and the oxygen atoms of the calix[6]-wheels. Analogous results were obtained when

• minimum-energy structure of (4+)36 obtained by molecular mechanics calculations (Figure 8). As it is known [17][18], the threading of directional (or constitutionally asymmetric) alkylbenzylammonium axles with directional calixarene-wheels, could generate two diastereoisomeric pseudo[2]rotaxanes (Figure 9

• ); (c) DOSY spectra of 6 (black line) and a 1:1 mixture of 6 and 7+·TFPB− (red line). Inset: structures of the triple-calix[6]arene 6 and 7+6 pseudo[2]rotaxane obtained by molecular mechanics calculations. 1H NMR titration of 6 with 7+·TFPB– (CDCl3 , 298 K, 600 MHz). Significant portions of the 1H NMR

Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of cis-2-halocyclohexylamines

• Camila B. Francisco,
• Cleverton S. Fernandes,
• Ulisses Z. de Melo,
• Roberto Rittner,
• Gisele F. Gauze and
• Ernani A. Basso

Beilstein J. Org. Chem. 2019, 15, 818–829, doi:10.3762/bjoc.15.79

• repulsion [32]. Another parameter evaluated was the total electrostatic energy, Eelect, according molecular mechanics calculations employing the Amber force field GAFF [33]. So, after the deletion of hyperconjugative interactions, we should analyze the delocalization energy, where higher values indicate

• function LanL2DZ-ECP was employed for the iodine atom. Solvation calculations were performed in dichloromethane and methanol, with the the implicit model IEF-PCM and the description of the molecular cavity through Bondi’s atomic radii. Molecular Mechanics calculations were performed using the software

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• , 46.9, 55.3, 99.5, 101.6, 114.3, 116.2, 123.1, 126.7, 127.3, 146.7, 147.0, 156.6, 156.8, 159.8; HRMS–ESI (m/z): [M + H]+ calcd for C20H22N7O, 376.1880; found, 376.1887. Quantum chemical calculations The initial molecular geometries were generated by using a molecular mechanics method (force field MMF94

• , steepest descent algorithm) and systematic conformational analysis as implemented in Avogadro 1.1.1 software. The minimum energy conformers found by molecular mechanics were further optimized with the Gaussian 09 program package [57] by the means of DFT using B3LYP exchange–correlation hybrid functional

Coordination-driven self-assembly vs dynamic covalent chemistry: versatile methods for the synthesis of molecular metallarectangles

• Li-Li Ma,
• Jia-Qin Han,
• Wei-Guo Jia and
• Ying-Feng Han

Beilstein J. Org. Chem. 2018, 14, 2027–2034, doi:10.3762/bjoc.14.178

• tetracationic half-sandwich rhodium metallarectangles [3a – 4OTf]4+ (left) and [3b – 4OTf]4+ (right). Optimized structures of the charged metallarectangles 3a (top) and 3b (bottom), optimized with the molecular mechanics force field. The graphics were produced using the Diamond software package. Colors: C, gray

Host–guest complexes of conformationally flexible C-hexyl-2-bromoresorcinarene and aromatic N-oxides: solid-state, solution and computational studies

• Rakesh Puttreddy,
• Ngong Kodiah Beyeh,
• S. Maryamdokht Taimoory,
• Daniel Meister,
• John F. Trant and
• Kari Rissanen

Beilstein J. Org. Chem. 2018, 14, 1723–1733, doi:10.3762/bjoc.14.146

• effort to better understand the host–guest interactions and the potentials of the secondary lower-rim binding mode, molecular mechanics (OPLS-2005) [42] calculations were performed on complexes, 3@BrC2, 3@BrC3 and 3@BrC6 using Jaguar (Schrödinger) [43][44]. Consequently, the structures are modelled for

Steric “attraction”: not by dispersion alone

• Ganna Gryn’ova and
• Clémence Corminboeuf

Beilstein J. Org. Chem. 2018, 14, 1482–1490, doi:10.3762/bjoc.14.125

• model based on a promolecule augmented with point charges [53] and a screened charge model with a molecular mechanics outer density screening algorithm [54]. In the context of hydrocarbon chemistry, the need to include charge penetration in FFs when modeling π–π and CH···π interactions in unsaturated

• with graphite [61]. However, the importance of introducing the penetration effects in the molecular mechanics united-atom and all-atom force fields, commonly employed to describe the aliphatic systems [62][63], including such industrially relevant representatives as graphane [64] and polyethylene [65

• would lead to elongated intermolecular distances. This might potentially be one of the reasons why the molecular mechanics force fields, commonly applied to aliphatics (see Introduction), significantly underestimate the liquid density and vapor pressure for long chain linear alkanes [70] and branched

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

• geometric calculations of the MDs were performed using the program VMD 1.9.2 [36]. Moreover, the molecular mechanics/generalized Born surface area (MM/GBSA) method [49], was used for a theoritical estimation of the binding free energy ΔGGB of the inclusion complex. The calculations were performed using

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 effect of cyclodextrin complexation on the solubility and photostability of nerolidol as pure compound and as main constituent of cabreuva essential oil

• Joyce Azzi,
• Pierre-Edouard Danjou,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2017, 13, 835–844, doi:10.3762/bjoc.13.84

• the solid inclusion complexes, respectively. Molecular modelling studies Molecular mechanics simulation was done using the Macromodel-MMFFs force field in the presence of water (GB/SA implicit model) as implemented in the Schrodinger software (release 2014). The CD hosts were based on a non-distorted

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

• . DrugScore uses knowledge-based potential functions to predict binding affinity [116]. Other knowledge-based scoring functions include the PMF (Potential of Mean Force) [117] and Bleep [118]. Force-field-based scoring functions Force-field based energy functions are developed using classical molecular

• mechanics. Electrostatic (coulombic) interactions and van der Waals interactions (Lennard-Jones potential) contribute to the interaction energy between a target–ligand complex. Two of the most widely used molecular mechanical force-fields are CHARMM [119] (Chemistry at HARvard Macromolecular Mechanics) and

Experimental and theoretical investigations into the stability of cyclic aminals

• Edgar Sawatzky,
• Antonios Drakopoulos,
• Martin Rölz,
• Christoph Sotriffer,
• Bernd Engels and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 2280–2292, doi:10.3762/bjoc.12.221

• investigations into their stability towards hydrolysis depending on the pH value are lacking. Results: A set of cyclic aminals was synthesized and their stability quantified by kinetic measurements. Steric and electronic effects were investigated by choosing appropriate groups. Both molecular mechanics (MM) and

• of these valuable synthetic intermediates and natural products, appropriate conditions have to be chosen and for application as drug molecules their sensitivity towards hydrolysis has to be taken into account. Keywords: hydrolysis; kinetics; molecular mechanics; natural products; quantum mechanics

• using Molecular Mechanics (MM). For this purpose, the conformer of minimal energy for compounds 9b and 13b,c was kept frozen, while the N-side groups were changed into a methyl residue. The resulting structures were therefore identical with compound 8a, thus differences in potential energy are

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• analysis showed up some fascinating differences between these steroids that could be related to their structures derived from molecular mechanics. This topic was not however the greatest, lasting memory from my Ph.D. studies. Neither was manually dredging the Chemical Abstracts for each literature search