In the Quest for a Stable Triplet State in Small Polyaromatic Hydrocarbons : An In-Silico Tool for Rational Design and Prediction

2019 ◽  
Author(s):  
Madhumita Rano ◽  
Sumanta K Ghosh ◽  
Debashree Ghosh
Keyword(s):  
Triplet State ◽  
Small Molecules ◽  
In Silico ◽  
Qualitative Agreement ◽  
Rational Design ◽  
Polyaromatic Hydrocarbons ◽  
Spin Hamiltonian ◽  
Spin Frustration ◽  
Computationally Efficient ◽  
High Level

<div>Combining the roles of spin frustration and geometry of odd and even numbered rings in polyaromatic hydrocarbons (PAHs), we design small molecules that show exceedingly small singlet-triplet gaps and stable triplet ground states. Furthermore, a computationally efficient protocol with a model spin Hamiltonian is shown to be capable of qualitative agreement with respect to high level multireference calculations and therefore, can be used for fast molecular discovery and screening.</div>

In the Quest for a Stable Triplet State in Small Polyaromatic Hydrocarbons : An In-Silico Tool for Rational Design and Prediction

2019 ◽  
Author(s):  
Madhumita Rano ◽  
Sumanta K Ghosh ◽  
Debashree Ghosh
Keyword(s):  
Triplet State ◽  
Small Molecules ◽  
In Silico ◽  
Qualitative Agreement ◽  
Rational Design ◽  
Polyaromatic Hydrocarbons ◽  
Spin Hamiltonian ◽  
Spin Frustration ◽  
Computationally Efficient ◽  
High Level

<div>Combining the roles of spin frustration and geometry of odd and even numbered rings in polyaromatic hydrocarbons (PAHs), we design small molecules that show exceedingly small singlet-triplet gaps and stable triplet ground states. Furthermore, a computationally efficient protocol with a model spin Hamiltonian is shown to be capable of qualitative agreement with respect to high level multireference calculations and therefore, can be used for fast molecular discovery and screening.</div>

scholarly journals In the quest for a stable triplet state in small polyaromatic hydrocarbons: an in silico tool for rational design and prediction

2019 ◽  
Vol 10 (40) ◽  
pp. 9270-9276 ◽  
Author(s):  
Madhumita Rano ◽  
Sumanta K. Ghosh ◽  
Debashree Ghosh
Keyword(s):  
Triplet State ◽  
Small Molecules ◽  
In Silico ◽  
Rational Design ◽  
Polyaromatic Hydrocarbons ◽  
Ground States ◽  
Spin Frustration

Spin frustration plays a major role in reduction of singlet-triplet gaps and that is leveraged to design small molecules with stable triplet ground states.

scholarly journals Binding Ensembles of p53-MDM2 Peptide Inhibitors by Combining Bayesian Inference and Atomistic Simulations

Molecules ◽  
2021 ◽  
Vol 26 (1) ◽  
pp. 198
Author(s):  
Lijun Lang ◽  
Alberto Perez
Keyword(s):  
Bayesian Inference ◽  
Virtual Screening ◽  
Statistical Mechanics ◽  
Small Molecules ◽  
Rational Design ◽  
Driving Forces ◽  
Peptide Inhibitors ◽  
Atomistic Simulations ◽  
Binding Mechanism ◽  
Intrinsically Disordered

Designing peptide inhibitors of the p53-MDM2 interaction against cancer is of wide interest. Computational modeling and virtual screening are a well established step in the rational design of small molecules. But they face challenges for binding flexible peptide molecules that fold upon binding. We look at the ability of five different peptides, three of which are intrinsically disordered, to bind to MDM2 with a new Bayesian inference approach (MELD × MD). The method is able to capture the folding upon binding mechanism and differentiate binding preferences between the five peptides. Processing the ensembles with statistical mechanics tools depicts the most likely bound conformations and hints at differences in the binding mechanism. Finally, the study shows the importance of capturing two driving forces to binding in this system: the ability of peptides to adopt bound conformations (ΔGconformation) and the interaction between interface residues (ΔGinteraction).

scholarly journals Rational design of potent anti-COVID-19 main protease drugs: An extensive multi-spectrum in silico approach

2021 ◽  
Vol 330 ◽  
pp. 115636
Author(s):  
Sajjad Ahmad ◽  
Yasir Waheed ◽  
Saba Ismail ◽  
Muzammil Hasan Najmi ◽  
Jawad Khaliq Ansari
Keyword(s):  
In Silico ◽  
Rational Design ◽  
Main Protease

scholarly journals How metallylenes activate small molecules

2021 ◽  
Vol 12 (12) ◽  
pp. 4526-4535
Author(s):  
Pascal Vermeeren ◽  
Michael T. Doppert ◽  
F. Matthias Bickelhaupt ◽  
Trevor A. Hamlin
Keyword(s):  
Small Molecules ◽  
Quantum Chemical ◽  
Rational Design ◽  
Chemical Analyses

Quantum chemical analyses reveal how model metallylene catalysts activate H2. This is the first step towards the rational design of metallylenes for the activation of small molecules and subsequent reactions.

Rational Design of Macrolides by Virtual Screening of Combinatorial Libraries Generated through in Silico Manipulation of Polyketide Synthases

2006 ◽  
Vol 49 (6) ◽  
pp. 2077-2087 ◽  
Author(s):  
Sergey B. Zotchev ◽  
Alla V. Stepanchikova ◽  
Anastasia P. Sergeyko ◽  
Boris N. Sobolev ◽  
Dmitrii A. Filimonov ◽  
...  
Keyword(s):  
Virtual Screening ◽  
In Silico ◽  
Rational Design ◽  
Combinatorial Libraries ◽  
Polyketide Synthases

scholarly journals A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

2016 ◽  
Vol 12 ◽  
pp. 125-138 ◽  
Author(s):  
Steven C Zimmerman
Keyword(s):  
Small Molecules ◽  
Supramolecular Chemistry ◽  
Myotonic Dystrophy ◽  
Small Molecule ◽  
Early Life ◽  
Rational Design ◽  
Early Experience ◽  
Therapeutic Agents ◽  
Early Career ◽  
Molecular Tweezers

This review summarizes part of the author’s research in the area of supramolecular chemistry, beginning with his early life influences and early career efforts in molecular recognition, especially molecular tweezers. Although designed to complex DNA, these hosts proved more applicable to the field of host–guest chemistry. This early experience and interest in intercalation ultimately led to the current efforts to develop small molecule therapeutic agents for myotonic dystrophy using a rational design approach that heavily relies on principles of supramolecular chemistry. How this work was influenced by that of others in the field and the evolution of each area of research is highlighted with selected examples.

scholarly journals GENETIC INVOLVEMENT OF INTERLEUKIN 4 FOR ASTHMA AND IDENTIFICATION OF POTENTIAL PHYTOCHEMICAL SCAFFOLD THROUGH MOLECULAR DOCKING STUDIES

2018 ◽  
Vol 10 (1) ◽  
pp. 43 ◽  
Author(s):  
S. Sarithamol ◽  
Divya V. ◽  
Sunitha V. R. ◽  
Suchitra Surendran ◽  
V. L. Pushpa ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Small Molecules ◽  
In Silico ◽  
Mutational Analysis ◽  
Chromosome Region ◽  
Specific Treatment ◽  
Docking Studies ◽  
Interleukin 4 ◽  
Receptor Interaction ◽  
Drug Candidates

Objective: Interleukin 4, an important cytokine, has the major role in the immunomodulatory responses associated with asthma. The present study focused on the involvement of single nucleotide polymorphism variation (SNP) of interleukin 4 (IL4) in the development of disease, asthma and designing small molecules for the inhibition of IL4 through in silico strategy.Methods: Identification of disease causing SNP will be a wise approach towards the phenotype specific treatment. A human origin deleterious no synonymous SNP of IL4 were found out in the chromosome region 5q31-q33 (rs199929962) (T/C). Proteins of the corresponding nucleotide variation were identified and were subjected to characterization studies for selecting the most appropriate one for further mutational analysis and molecular docking studies.Results: Influence of microbes on SNP variation of IL4 gene leading to asthma was found to be insignificant by metagenomic studies. Gene responsive drugs were identified through environmental factor analysis. The drug candidates including corticosteroids were subjected to protein interaction studies by in silico means. The pharmacophoric feature derived from drug receptor interaction was utilized for virtual screening on a dataset of anti-inflammatory phytomolecules. The scaffolds of ellagic acid and quercetin were identified as potential nonsteroidal entities which can shield the asthmatic activities.Conclusion: Developing small molecules using these scaffolds taking interleukin 4 as a target will be an adequate solution for steroid resistant asthma.

scholarly journals Truncated Non-Nuclear Transposable Elements in Grapevine: A Mini Review

2019 ◽  
Vol 50 (4) ◽  
pp. 219-227
Author(s):  
A.V. Milovanov ◽  
J. Tello ◽  
U.C.M. Anhalt ◽  
A. Forneck
Keyword(s):  
Gene Transfer ◽  
Mitochondrial Genome ◽  
Transposable Elements ◽  
Vitis Vinifera ◽  
In Silico ◽  
Gene Evolution ◽  
High Rate ◽  
Miniature Inverted Transposable Elements ◽  
High Level ◽  
Inner Region

Abstract In this mini-review we present insight to the non-nuclear transposable elements and in silico analysis of miniature inverted transposable elements (MITEs) in the grapevine mitochondrial genome. Here we report the identification of 17 truncated sequences in grapevine (Vitis vinifera L.) mitochondrial genome which expectedly belongs to the four ancient transposon families (hAT, Tc1Mariner, Mutator and PIF/Harbinger). Some sequences with a high rate of homology in chloroplast and nuclear genomes were also identified. Thus, it suggests the intercellular gene transfer between these three organelles. These partial sequences showed a high level of similitude with full MITE sequences, and they were found in their inner region, supporting their MITE origin. Further analysis revealed these sequences in other life kingdoms (including eubacteria and archaea), which indicates their ancient origin. Further research showed that 13 out of the 17 sequences are conserved domains of the genes where they are located, suggesting their contribution to gene evolution. Therefore, we suppose that more studies of nature, origin and functional meaning of these sequences and their fusion with genes are necessary. In the light of our observations it will be useful for further studies of V. vinifera genome organizing and systematics, as well as for other species.

scholarly journals Podophyllotoxin and Quercetin in Silico Derivatives Docking Analysis with Cyclooxygenase-2 and Aminopeptidase-N

2021 ◽  
Author(s):  
A.E. Manukyan ◽  
A.A. Hovhannisyan
Keyword(s):  
In Silico ◽  
Biological Activities ◽  
Three Dimensional ◽  
Aminopeptidase N ◽  
Docking Analysis ◽  
Quercetin Derivatives ◽  
Pubchem Database ◽  
A Cell ◽  
Cox 2 ◽  
High Level

ABSTRACTThe cyclooxygenase (COX) enzymes are tumor markers, the inhibition of which can be used in the prevention and therapy of carcinogenesis. It was found that COX-2 IS considered as targets for tumor inhibition. Aminopeptidase N (APN) is a type II membrane-bound metalloprotease associated with cancer, being identified as a cell marker on the surface of malignant myeloid cells and reached a high level of expression in progressive tumors. In anticancer therapy, plant compounds are considered that can inhibit their activity. Modeling of the COX-2 and APN enzymes was carried out on the basis of molecular models of three-dimensional structures from the PDB database [PDB ID: 5f19, 4fyq] RCSB. For docking analysis, 3D ligand models were created using MarvinSketch based on the PubChem database [CID: 5280343, 5281654]. In silico experiments, for the first time, revealed the possible interaction and inhibition of COX-2 and APN by quercetin and quercetin derivatives. Aspirin and Marimastat were taken to compare the results. Possible biological activities and possible side effects of the ligands have been identified.

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