Crystallography based investigation of weak interaction for drug designing against COVID-19

2021 ◽  
Author(s):  
Nayim Sepay ◽  
Pranab C. Saha ◽  
Zarrin Shahzadi ◽  
Aratrika Chakraborty ◽  
Umesh Chandra Halder
Keyword(s):  
Small Molecules ◽  
Weak Interaction ◽  
Protein Function ◽  
Complete Understanding ◽  
Drug Designing ◽  
Non Covalent Interactions ◽  
Covalent Interactions

Interactions between protein-small molecules plays an important roles in inhibition of protein function. However, lack of proper knowledge of non-covalent interactions acts as a barrier towards complete understanding of factors...

Insight on the Factors Controlling the Equilibrium of Allylic Azides

2019 ◽  
Author(s):  
Margarita Vallejos ◽  
Guillermo Labadie
Keyword(s):  
Weak Interaction ◽  
Density Functional ◽  
Equilibrium Mixture ◽  
Hydroxyl Group ◽  
Functional Theory ◽  
Non Covalent Interactions ◽  
Allylic Azides ◽  
Covalent Interactions ◽  
Insight Into ◽  
Good Linear Correlation

<p>Several allylic azides with different double bond substitution were studied to understand the factors governing their equilibrium using density functional theory along with quantum theory of atoms in molecules, Non-covalent Interactions and Natural Bond Orbitals approaches. The results showed the hydroxyl group or heteroatoms in allylic azides interact with the molecule through an electrostatic weak interaction in each pair of regioisomers. The equilibrium shifts of substituted allylic azides, compared to non-substituted allylic azides, are not attributed to the presence of specific interactions, such as hydrogen bond. The observed equilibrium shifts stem mainly from the strengthening and weakening of negative hyperconjugative interactions, which is affected by the weak interaction involving the proximal substituent in each regioisomer. A good linear correlation was obtained between the hyperconjugative energies of pC=C→s*<i>Z</i><sub>b</sub> interactions and the calculated percentages of secondary azide and tertiary azides in the equilibrium mixture. Also, the effect of aromatic ring substituent was analysed using such approaches. This study not only provides insight into the factor controlling the stabilities of the substituted allylic azides, but also settle the basis to predict the regioisomer predominance in the equilibrium mixture.</p>

scholarly journals An Oncometabolite Isomer Rapidly Induces A Pathophysiological Protein Modification

2020 ◽  
Author(s):  
Sarah E. Bergholtz ◽  
Chloe A. Briney ◽  
Susana S. Najera ◽  
Minervo Perez ◽  
W. Marston Linehan ◽  
...  
Keyword(s):  
Protein Function ◽  
Protein Modification ◽  
Living Cells ◽  
Cellular Assays ◽  
Non Covalent Interactions ◽  
Regulate Protein ◽  
Chemical Strategy ◽  
Covalent Interactions

ABSTRACTMetabolites regulate protein function via covalent and non-covalent interactions. However, manipulating these interactions in living cells remains a major challenge. Here we report a chemical strategy for inducing cysteine S-succination, a non-enzymatic posttranslational modification derived from the oncometabolite fumarate. Using a combination of antibody-based detection and kinetic assays we benchmark the in vitro and cellular reactivity of two novel S-succination “agonists,” maleate and 2-bromosuccinate. Cellular assays reveal maleate to be a more potent and less toxic inducer of S-succination which can activate KEAP1-NRF2 signaling in living cells. By enabling the cellular reconstitution of an oncometabolite-protein interaction with physiochemical accuracy and minimal toxicity, this study provides a methodological basis for better understanding the signaling role of metabolites in disease.

Insight on the Factors Controlling the Equilibrium of Allylic Azides

2019 ◽  
Author(s):  
Margarita Vallejos ◽  
Guillermo Labadie
Keyword(s):  
Weak Interaction ◽  
Density Functional ◽  
Equilibrium Mixture ◽  
Hydroxyl Group ◽  
Functional Theory ◽  
Non Covalent Interactions ◽  
Allylic Azides ◽  
Covalent Interactions ◽  
Insight Into ◽  
Good Linear Correlation

<p>Several allylic azides with different double bond substitution were studied to understand the factors governing their equilibrium using density functional theory along with quantum theory of atoms in molecules, Non-covalent Interactions and Natural Bond Orbitals approaches. The results showed the hydroxyl group or heteroatoms in allylic azides interact with the molecule through an electrostatic weak interaction in each pair of regioisomers. The equilibrium shifts of substituted allylic azides, compared to non-substituted allylic azides, are not attributed to the presence of specific interactions, such as hydrogen bond. The observed equilibrium shifts stem mainly from the strengthening and weakening of negative hyperconjugative interactions, which is affected by the weak interaction involving the proximal substituent in each regioisomer. A good linear correlation was obtained between the hyperconjugative energies of pC=C→s*<i>Z</i><sub>b</sub> interactions and the calculated percentages of secondary azide and tertiary azides in the equilibrium mixture. Also, the effect of aromatic ring substituent was analysed using such approaches. This study not only provides insight into the factor controlling the stabilities of the substituted allylic azides, but also settle the basis to predict the regioisomer predominance in the equilibrium mixture.</p>

scholarly journals Effect of Abolition of Intersubunit Salt Bridges on Allosteric Protein Structural Dynamics

2021 ◽  
Author(s):  
Hyotcherl Ihee ◽  
Minseo Choi ◽  
Jong Goo Kim ◽  
Srinivasan Muniyappan ◽  
Hanui Kim ◽  
...  
Keyword(s):  
Structural Dynamics ◽  
Protein Function ◽  
Crucial Role ◽  
Salt Bridge ◽  
Structural Factors ◽  
Salt Bridges ◽  
Protein Structural Dynamics ◽  
Non Covalent Interactions ◽  
Covalent Interactions ◽  
Allosteric Protein

Salt bridge, one of the representative structural factors established by non-covalent interactions, plays a crucial role in stabilizing the structure and regulating the protein function, but its role in dynamic...

scholarly journals Chitosan Functionalization: Covalent and Non-Covalent Interactions and Their Characterization

Polymers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 4118
Author(s):  
Laura Nicolle ◽  
Céline M. A. Journot ◽  
Sandrine Gerber-Lemaire
Keyword(s):  
Mechanical Properties ◽  
Small Molecules ◽  
State Of The Art ◽  
Low Cost ◽  
Special Focus ◽  
Chemical Modifications ◽  
Research Fields ◽  
Non Covalent Interactions ◽  
Covalent Modifications ◽  
Covalent Interactions

Chitosan (CS) is a natural biopolymer that has gained great interest in many research fields due to its promising biocompatibility, biodegradability, and favorable mechanical properties. The versatility of this low-cost polymer allows for a variety of chemical modifications via covalent conjugation and non-covalent interactions, which are designed to further improve the properties of interest. This review aims at presenting the broad range of functionalization strategies reported over the last five years to reflect the state-of-the art of CS derivatization. We start by describing covalent modifications performed on the CS backbone, followed by non-covalent CS modifications involving small molecules, proteins, and metal adjuvants. An overview of CS-based systems involving both covalent and electrostatic modification patterns is then presented. Finally, a special focus will be given on the characterization techniques commonly used to qualify the composition and physical properties of CS derivatives.

scholarly journals On the Use of Popular Basis Sets: Impact of the Intramolecular Basis Set Superposition Error

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3810 ◽  
Author(s):  
Ángel Vidal Vidal ◽  
Luis de Vicente Poutás ◽  
Olalla Nieto Faza ◽  
Carlos Silva López
Keyword(s):  
Small Molecules ◽  
Chemical Properties ◽  
Basis Set ◽  
Basis Sets ◽  
Basis Set Superposition Error ◽  
Large Molecules ◽  
Molecular Complexation ◽  
Non Covalent Interactions ◽  
Covalent Interactions ◽  
Structure Calculations

The magnitude of intramolecular basis set superposition error (BSSE) is revealed via computing systematic trends in molecular properties. This type of error is largely neglected in the study of the chemical properties of small molecules and it has historically been analyzed just in the study of large molecules and processes dominated by non-covalent interactions (typically dimerization or molecular complexation and recognition events). In this work we try to provide proof of the broader prevalence of this error, which permeates all types of electronic structure calculations, particularly when employing insufficiently large basis sets.

NON COVALENT INTERACTIONS IN LARGE DIAMONDOID DIMERS IN THE GAS PHASE - A MICROWAVE STUDY

2017 ◽  
Author(s):  
Cristobal Perez ◽  
Melanie Schnell ◽  
Peter Schreiner ◽  
Norbert Mitzel ◽  
Yury Vishnevskiy ◽  
...  
Keyword(s):  
Gas Phase ◽  
Non Covalent Interactions ◽  
Covalent Interactions

Vapour Pressure Isotope Effect on Evaporation from Pure Organic Phases - a PIMD Approach

2020 ◽  
Author(s):  
Luis Vasquez ◽  
Agnieszka Dybala-Defratyka
Keyword(s):  
Path Integral ◽  
Vapour Pressure ◽  
Density Functional ◽  
Isotope Effects ◽  
Tight Binding ◽  
Decomposition Analysis ◽  
Energy Decomposition Analysis ◽  
Special Importance ◽  
Non Covalent Interactions ◽  
Covalent Interactions

<p></p><p>Very often in order to understand physical and chemical processes taking place among several phases fractionation of naturally abundant isotopes is monitored. Its measurement can be accompanied by theoretical determination to provide a more insightful interpretation of observed phenomena. Predictions are challenging due to the complexity of the effects involved in fractionation such as solvent effects and non-covalent interactions governing the behavior of the system which results in the necessity of using large models of those systems. This is sometimes a bottleneck and limits the theoretical description to only a few methods.<br> In this work vapour pressure isotope effects on evaporation from various organic solvents (ethanol, bromobenzene, dibromomethane, and trichloromethane) in the pure phase are estimated by combining force field or self-consistent charge density-functional tight-binding (SCC-DFTB) atomistic simulations with path integral principle. Furthermore, the recently developed Suzuki-Chin path integral is tested. In general, isotope effects are predicted qualitatively for most of the cases, however, the distinction between position-specific isotope effects observed for ethanol was only reproduced by SCC-DFTB, which indicates the importance of using non-harmonic bond approximations.<br> Energy decomposition analysis performed using the symmetry-adapted perturbation theory (SAPT) revealed sometimes quite substantial differences in interaction energy depending on whether the studied system was treated classically or quantum mechanically. Those observed differences might be the source of different magnitudes of isotope effects predicted using these two different levels of theory which is of special importance for the systems governed by non-covalent interactions.</p><br><p></p>

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