scholarly journals Explanation of the Formation of Complexes between Representatives of Oxazolidinones and HDAS-β-CD Using Molecular Modeling as a Complementary Technique to cEKC and NMR

2021 ◽  
Vol 22 (13) ◽  
pp. 7139
Author(s):  
Wojciech Bocian ◽  
Elżbieta Bednarek ◽  
Katarzyna Michalska

Molecular modeling (MM) results for tedizolid and radezolid with heptakis-(2,3-diacetyl-6-sulfo)-β-cyclodextrin (HDAS-β-CD) are presented and compared with the results previously obtained for linezolid and sutezolid. The mechanism of interaction of chiral oxazolidinone ligands belonging to a new class of antibacterial agents, such as linezolid, tedizolid, radezolid, and sutezolid, with HDAS-β-CD based on capillary electrokinetic chromatography (cEKC), nuclear magnetic resonance (NMR) spectroscopy, and MM methods was described. Principles of chiral separation of oxazolidinone analogues using charged single isomer derivatives of cyclodextrin by the cEKC method were presented, including the selection of the optimal chiral selector and separation conditions, complex stoichiometry, and binding constants, which provided a comprehensive basis for MM studies. In turn, NMR provided, where possible, direct information on the geometry of the inclusion complexes and also provided the necessary structural information to validate the MM calculations. Consequently, MM contributed to the understanding of the structure of diastereomeric complexes, the thermodynamics of complexation, and the visualization of their structures. The most probable mean geometries of the studied supramolecular complexes and their dynamics (geometry changes over time) were determined by molecular dynamics methods. Oxazolidinone ligands have been shown to complex mainly the inner part of cyclodextrin, while the external binding is less privileged, which is consistent with the conclusions of the NMR studies. Enthalpy values of binding of complexes were calculated using long-term molecular dynamics in explicit water as well as using molecular mechanics, the Poisson–Boltzmann or generalized Born, and surface area continuum solvation (MM/PBSA and MM/GBSA) methods. Computational methods predicted the effect of changes in pH and composition of the solution on the strength and complexation process, and it adapted the conditions selected as optimal during the cEKC study. By changing the dielectric constant in the MM/PBSA and MM/GBSA calculations, the effect of changing the solution to methanol/acetonitrile was investigated. A fairly successful attempt was made to predict the chiral separation of the oxazolidinones using the modified cyclodextrin by computational methods.

2019 ◽  
Vol 25 (31) ◽  
pp. 3339-3349 ◽  
Author(s):  
Indrani Bera ◽  
Pavan V. Payghan

Background: Traditional drug discovery is a lengthy process which involves a huge amount of resources. Modern-day drug discovers various multidisciplinary approaches amongst which, computational ligand and structure-based drug designing methods contribute significantly. Structure-based drug designing techniques require the knowledge of structural information of drug target and drug-target complexes. Proper understanding of drug-target binding requires the flexibility of both ligand and receptor to be incorporated. Molecular docking refers to the static picture of the drug-target complex(es). Molecular dynamics, on the other hand, introduces flexibility to understand the drug binding process. Objective: The aim of the present study is to provide a systematic review on the usage of molecular dynamics simulations to aid the process of structure-based drug design. Method: This review discussed findings from various research articles and review papers on the use of molecular dynamics in drug discovery. All efforts highlight the practical grounds for which molecular dynamics simulations are used in drug designing program. In summary, various aspects of the use of molecular dynamics simulations that underline the basis of studying drug-target complexes were thoroughly explained. Results: This review is the result of reviewing more than a hundred papers. It summarizes various problems that use molecular dynamics simulations. Conclusion: The findings of this review highlight how molecular dynamics simulations have been successfully implemented to study the structure-function details of specific drug-target complexes. It also identifies the key areas such as stability of drug-target complexes, ligand binding kinetics and identification of allosteric sites which have been elucidated using molecular dynamics simulations.


Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 4089
Author(s):  
Katarzyna Betlejewska-Kielak ◽  
Elżbieta Bednarek ◽  
Armand Budzianowski ◽  
Katarzyna Michalska ◽  
Jan K. Maurin

Racemic ketoprofen (KP) and β-cyclodextrin (β-CD) powder samples from co-precipitation (1), evaporation (2), and heating-under-reflux (3) were analysed using X-ray techniques and nuclear magnetic resonance (NMR) spectroscopy. On the basis of NMR studies carried out in an aqueous solution, it was found that in the samples obtained by methods 1 and 2, there were large excesses of β-CD in relation to KP, 10 and 75 times, respectively, while the sample obtained by method 3 contained equimolar amounts of β-CD and KP. NMR results indicated that KP/β-CD inclusion complexes were formed and the estimated binding constants were approximately 2400 M−1, showing that KP is quite strongly associated with β-CD. On the other hand, the X-ray single-crystal technique in the solid state revealed that the (S)-KP/β-CD inclusion complex with a stoichiometry of 2:2 was obtained as a result of heating-under-reflux, for which the crystal and molecular structure were examined. Among the methods used for the preparation of the KP/β-CD complex, only method 3 is suitable.


2020 ◽  
Vol 21 (20) ◽  
pp. 7702 ◽  
Author(s):  
Sofya I. Scherbinina ◽  
Philip V. Toukach

Analysis and systematization of accumulated data on carbohydrate structural diversity is a subject of great interest for structural glycobiology. Despite being a challenging task, development of computational methods for efficient treatment and management of spatial (3D) structural features of carbohydrates breaks new ground in modern glycoscience. This review is dedicated to approaches of chemo- and glyco-informatics towards 3D structural data generation, deposition and processing in regard to carbohydrates and their derivatives. Databases, molecular modeling and experimental data validation services, and structure visualization facilities developed for last five years are reviewed.


Author(s):  
Arturas Ziemys ◽  
Alessandro Grattoni ◽  
Jaskaran Gill ◽  
Mauro Ferrari

The interface of silica nanochannel of 10 nm was studied by molecular modeling and experimental methods. Molecular Dynamics study on glucose solution revealed that 2–3 nm of interface solution to silica walls has reduced glucose diffusivity. That reduction affects the effective diffusivity of glucose in silica nanochannel. Experimental results show Fickian-like release of glucose through 13 nm nanochannel. Molecular modeling and experimental results suggest that glucose is not sufficiently confined to possess non-Fickian behavior.


2021 ◽  
Author(s):  
SAGAR PATIL ◽  
MICHAEL OLAYA ◽  
PRATHAMESH DESHPANDE ◽  
MARIANNA MAIARÙ ◽  
GREGORY ODEGARD

This article details the molecular modeling of full and off-stoichiometry models of the DGEBF/DETDA epoxy system using Molecular Dynamics to predict the mechanical properties as a function of the crosslinking density. The Reactive Interface Force Field (IFF-R) is implemented in this work to simulate mechanical deformation. The “fix bond/react” command in LAMMPS is used to simulate crosslinking between epoxy monomers. The results show that the predicted mass density, volumetric shrinkage, and bulk modulus have a strong dependence on the stoichiometry of the epoxy.


2010 ◽  
Vol 82 (10) ◽  
pp. 1943-1955 ◽  
Author(s):  
Maksym Druchok ◽  
Vojko Vlachy

An explicit water molecular dynamics (MD) simulation is presented of a solution modeling aliphatic 6,6-ionene oligocations mixed with low-molecular-weight electrolytes. In all cases, the co-ions were sodium cations and the counterions were fluoride, chloride, bromide, or iodide anions. The simple point charge/extended (SPC/E) model was used to describe water. The results of the simulation at T = 278 K (the data for 298 K were obtained earlier) and T = 318 K are presented in the form of pair distributions between various atoms and/or between ions in the system. We were interested in how temperature variation modifies the ion-specific effects, revealed by the various pair distribution functions (PDFs). The results were compared with previous calculations for the less hydrophobic 3,3-ionene solutions. Simulations of 6,6-ionene solutions containing mixtures of fluoride and iodide counter-ions at T = 298 K were also presented.


2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Salah Belaidi ◽  
Dalal Harkati

Conformational analysis of 18-ring membered macrolactones has been carried out using molecular mechanics calculations and molecular dynamics. A high conformational flexibility of macrolactones was obtained, and an important stereoselectivity was observed for the complexed macrolides. For 18d macrolactone, which was presented by a most favored conformer with 20.1% without complex, it was populated with 50.1% in presence of Fe(CO)3.


2018 ◽  
Vol 122 (36) ◽  
pp. 8560-8569 ◽  
Author(s):  
Ewelina Bolimowska ◽  
Franca Castiglione ◽  
Julien Devemy ◽  
Helene Rouault ◽  
Andrea Mele ◽  
...  

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