scholarly journals Solvent effects on the properties of hyperbranched polythiophenes

2016 ◽  
Vol 18 (35) ◽  
pp. 24610-24619
Author(s):  
Juan Torras ◽  
David Zanuy ◽  
David Aradilla ◽  
Carlos Alemán
Keyword(s):  
Solvent Effects ◽  
Md Simulations ◽  
Conformational Flexibility ◽  
Explicit Solvent ◽  
Different Types ◽  
Solvent Molecules

QM/MM-MD simulations of dendrimers using explicit solvent molecules capture the conformational flexibility and microfluctuations induced by different types of solvents.

scholarly journals Beyond Continuum Solvent Models in Computational Homogeneous Catalysis

2021 ◽  
Author(s):  
Gantulga Norjmaa ◽  
Gregori Ujaque ◽  
Agustí Lledós
Keyword(s):  
Homogeneous Catalysis ◽  
Solvent Effects ◽  
Solvent Polarity ◽  
Quantum Mechanical ◽  
Solvent Models ◽  
Quantum Mechanical Description ◽  
Explicit Solvent ◽  
Solvent Dynamics ◽  
Solvent Molecules ◽  
Continuum Solvent Models

AbstractIn homogeneous catalysis solvent is an inherent part of the catalytic system. As such, it must be considered in the computational modeling. The most common approach to include solvent effects in quantum mechanical calculations is by means of continuum solvent models. When they are properly used, average solvent effects are efficiently captured, mainly those related with solvent polarity. However, neglecting atomistic description of solvent molecules has its limitations, and continuum solvent models all alone cannot be applied to whatever situation. In many cases, inclusion of explicit solvent molecules in the quantum mechanical description of the system is mandatory. The purpose of this article is to highlight through selected examples what are the reasons that urge to go beyond the continuum models to the employment of micro-solvated (cluster-continuum) of fully explicit solvent models, in this way setting the limits of continuum solvent models in computational homogeneous catalysis. These examples showcase that inclusion of solvent molecules in the calculation not only can improve the description of already known mechanisms but can yield new mechanistic views of a reaction. With the aim of systematizing the use of explicit solvent models, after discussing the success and limitations of continuum solvent models, issues related with solvent coordination and solvent dynamics, solvent effects in reactions involving small, charged species, as well as reactions in protic solvents and the role of solvent as reagent itself are successively considered.

scholarly journals In Silico Design and Selection of New Tetrahydroisoquinoline-Based CD44 Antagonist Candidates

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1877
Author(s):  
Angel J. Ruiz-Moreno ◽  
Atilio Reyes-Romero ◽  
Alexander Dömling ◽  
Marco A. Velasco-Velázquez
Keyword(s):  
Md Simulations ◽  
Binding Mode ◽  
Cancer Therapies ◽  
Cd44 Isoforms ◽  
Computational Docking ◽  
Explicit Solvent ◽  
Anti Cancer ◽  
Different Types ◽  
Target Binding ◽  
Selection Of

CD44 promotes metastasis, chemoresistance, and stemness in different types of cancer and is a target for the development of new anti-cancer therapies. All CD44 isoforms share a common N-terminal domain that binds to hyaluronic acid (HA). Herein, we used a computational approach to design new potential CD44 antagonists and evaluate their target-binding ability. By analyzing 30 crystal structures of the HA-binding domain (CD44HAbd), we characterized a subdomain that binds to 1,2,3,4-tetrahydroisoquinoline (THQ)-containing compounds and is adjacent to residues essential for HA interaction. By computational combinatorial chemistry (CCC), we designed 168,190 molecules and compared their conformers to a pharmacophore containing the key features of the crystallographic THQ binding mode. Approximately 0.01% of the compounds matched the pharmacophore and were analyzed by computational docking and molecular dynamics (MD). We identified two compounds, Can125 and Can159, that bound to human CD44HAbd (hCD44HAbd) in explicit-solvent MD simulations and therefore may elicit CD44 blockage. These compounds can be easily synthesized by multicomponent reactions for activity testing and their binding mode, reported here, could be helpful in the design of more potent CD44 antagonists.

scholarly journals Conformational Ensembles by NMR and MD Simulations in Model Heptapeptides with Select Tri-Peptide Motifs

2021 ◽  
Vol 22 (3) ◽  
pp. 1364
Author(s):  
V. V. Krishnan ◽  
Timothy Bentley ◽  
Alina Xiong ◽  
Kalyani Maitra
Keyword(s):  
Principal Component ◽  
Md Simulations ◽  
Conformational Space ◽  
Random Coil ◽  
Radius Of Gyration ◽  
Small Peptides ◽  
Conformational Ensembles ◽  
Solution State ◽  
Peptide Motifs ◽  
Explicit Solvent

Both nuclear magnetic resonance (NMR) and molecular dynamics (MD) simulations are routinely used in understanding the conformational space sampled by peptides in the solution state. To investigate the role of single-residue change in the ensemble of conformations sampled by a set of heptapeptides, AEVXEVG with X = L, F, A, or G, comprehensive NMR, and MD simulations were performed. The rationale for selecting the particular model peptides is based on the high variability in the occurrence of tri-peptide E*L between the transmembrane β-barrel (TMB) than in globular proteins. The ensemble of conformations sampled by E*L was compared between the three sets of ensembles derived from NMR spectroscopy, MD simulations with explicit solvent, and the random coil conformations. In addition to the estimation of global determinants such as the radius of gyration of a large sample of structures, the ensembles were analyzed using principal component analysis (PCA). In general, the results suggest that the -EVL- peptide indeed adopts a conformational preference that is distinctly different not only from a random distribution but also from other peptides studied here. The relatively straightforward approach presented herein could help understand the conformational preferences of small peptides in the solution state.

scholarly journals Supramolecular architectures of 4-hydroxytetraphenylporphyrin with aza-donors

2014 ◽  
Vol 70 (a1) ◽  
pp. C554-C554 ◽  
Author(s):  
Purnendu Nandy ◽  
V. Pedireddi
Keyword(s):  
Three Dimensional ◽  
Molecular Complexes ◽  
Hydroxyl Groups ◽  
X Ray Diffraction ◽  
X Ray ◽  
Supramolecular Architectures ◽  
Detailed Structural Analysis ◽  
Different Types ◽  
Solvent Molecules ◽  
Molecular Adducts

Molecular adducts of 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (1) with aza-donors like 4,4'-bipyridine (a), 1,2-bis(4-pyridyl)ethane (b), trans-1,2-bis(4-pyridyl)ethylene (c), 4,4'-trimethylene-dipyridine (d), phenazine (e), 1,10-phenanthroline (f), 1,7-phenanthroline (g) and 4,7-phenanthroline (h) have been prepared. All the molecular complexes are crystallized along with the solvent of crystallization, except in the complex with the aza-donor b. Detailed structural analysis of the obtained complexes has been carried out by single crystal X-ray diffraction. The three dimensional structures of the molecular adducts are facilitated by directional hydrogen bonding features of hydroxyl groups with aza donors as well as solvent molecules, leading to the formation of different types of supramolecular architectures like sheets, tapes, host-guest assembly etc. For example, in the complex of 1 and aza donor a, which crystallizes as a hydrate, the porphyrin molecules interact with water and 4,4'-bipyridine through O-H...O and O-H...N hydrogen bonds, which leads to the formation of molecular sheets in two dimensional arrangement. An important noteworthy observation is that the molecular complexes are crystalline even after removal of the solvents by heating, as characterized by thermogravimetric analysis (TGA) and powder X-ray diffraction (PXRD). Further, all the complexes are found to be fluorescence sensitive, perhaps due to the porphyrin molecules.

scholarly journals Machine Learning Guided Approach for Studying Solvation Environments

2019 ◽  
Author(s):  
Yasemin Basdogan ◽  
Mitchell C. Groenenboom ◽  
Ethan Henderson ◽  
Sandip De ◽  
Susan Rempe ◽  
...  
Keyword(s):  
A Priori ◽  
Optimization Procedure ◽  
Low Energy ◽  
Free Energies ◽  
Continuum Approach ◽  
Explicit Solvent ◽  
Linear Dimensionality Reduction ◽  
Solvent Molecules ◽  
Dynamics Simulations ◽  
Solvation Free Energies

<div><div><div><p>Toward practical modeling of local solvation effects of any solute in any solvent, we report a static and all-quantum mechanics based cluster-continuum approach for calculating single ion solvation free energies. This approach uses a global optimization procedure to identify low energy molecular clusters with different numbers of explicit solvent molecules and then employs the Smooth Overlap for Atomic Positions (SOAP) kernel to quantify the similarity between different low energy solute environments. From these data, we use sketch-map, a non-linear dimensionality reduction algorithm, to obtain a two-dimensional visual representation of the similarity between solute environments in differently sized microsolvated clusters. Without needing either dynamics simulations or an a priori knowledge of local solvation structure of the ions, this approach can be used to calculate solvation free energies with errors within five percent of experimental measurements for most cases.</p></div></div></div>

scholarly journals Molecular Dynamics Simulation of Homo-DNA: The Role of Crystal Packing in Duplex Conformation

Crystals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 532
Author(s):  
Jonathan H. Sheehan ◽  
Jarrod A. Smith ◽  
Pradeep S. Pallan ◽  
Terry P. Lybrand ◽  
Martin Egli
Keyword(s):  
Crystal Structure ◽  
Molecular Dynamics ◽  
Nucleic Acid ◽  
Base Pair ◽  
Crystal Packing ◽  
Md Simulations ◽  
Conformational Flexibility ◽  
Dynamics Simulation ◽  
Dna Duplex ◽  
Solution Studies

The (4′→6′)-linked DNA homolog 2′,3′-dideoxy-β-D-glucopyranosyl nucleic acid (dideoxy-glucose nucleic acid or homo-DNA) exhibits stable self-pairing of the Watson–Crick and reverse-Hoogsteen types, but does not cross-pair with DNA. Molecular modeling and NMR solution studies of homo-DNA duplexes pointed to a conformation that was nearly devoid of a twist and a stacking distance in excess of 4.5 Å. By contrast, the crystal structure of the homo-DNA octamer dd(CGAATTCG) revealed a right-handed duplex with average values for helical twist and rise of ca. 15° and 3.8 Å, respectively. Other key features of the structure were strongly inclined base-pair and backbone axes in the duplex with concomitant base-pair slide and cross-strand stacking, and the formation of a dimer across a crystallographic dyad with inter-duplex base swapping. To investigate the conformational flexibility of the homo-DNA duplex and a potential influence of lattice interactions on its geometry, we used molecular dynamics (MD) simulations of the crystallographically observed dimer of duplexes and an isolated duplex in the solution state. The dimer of duplexes showed limited conformational flexibility, and key parameters such as helical rise, twist, and base-pair slide exhibited only minor fluctuations. The single duplex was clearly more flexible by comparison and underwent partial unwinding, albeit without significant lengthening. Thus, base stacking was preserved in the isolated duplex and two adenosines extruded from the stack in the dimer of duplexes were reinserted into the duplex and pair with Ts in a Hoogsteen mode. Our results confirmed that efficient stacking in homo-DNA seen in the crystal structure of a dimer of duplexes was maintained in the separate duplex. Therefore, lattice interactions did not account for the different geometries of the homo-DNA duplex in the crystal and earlier models that resembled inclined ladders with large base-pair separations that precluded efficient stacking.

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