Rational Design of Small Molecules to Implement Organic Quaternary Memory Devices

2015 ◽  
Vol 26 (1) ◽  
pp. 146-154 ◽  
Author(s):  
Qijian Zhang ◽  
Jinghui He ◽  
Hao Zhuang ◽  
Hua Li ◽  
Najun Li ◽  
...  
Keyword(s):  
Small Molecules ◽  
Rational Design ◽  
Memory Devices

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 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 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.

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.

Rational Design of Small Molecules for a Novel Class of Anti-Cancer Drugs using a Phenylalanine Library

2006 ◽  
pp. 459-460
Author(s):  
Lajos Gera ◽  
Daniel C. Chan ◽  
Laimute Taraseviciene-Stewart ◽  
Vitalija Simkeviciene ◽  
Paul A. Bunn ◽  
...  
Keyword(s):  
Small Molecules ◽  
Rational Design ◽  
Cancer Drugs ◽  
Anti Cancer

Fluorenone/carbazole based bipolar small molecules for non-volatile memory devices

2020 ◽  
Vol 78 ◽  
pp. 105584 ◽  
Author(s):  
Jia-Qin Yang ◽  
Li-Yu Ting ◽  
Ruopeng Wang ◽  
Jing-Yu Mao ◽  
Yi Ren ◽  
...  
Keyword(s):  
Small Molecules ◽  
Memory Devices ◽  
Non Volatile Memory ◽  
Volatile Memory

scholarly journals Boron(iii) β-diketonate-based small molecules for functional non-fullerene polymer solar cells and organic resistive memory devices

2020 ◽  
Vol 11 (42) ◽  
pp. 11601-11612
Author(s):  
Panpan Li ◽  
Quanbin Liang ◽  
Eugene Yau-Hin Hong ◽  
Chin-Yiu Chan ◽  
Yat-Hin Cheng ◽  
...  
Keyword(s):  
Solar Cells ◽  
Small Molecules ◽  
Polymer Solar Cells ◽  
Functional Materials ◽  
Memory Devices ◽  
Resistive Memory

Boron(iii) β-diketonates have been demonstrated to serve as multi-functional materials in NFA-based OPVs and organic resistive memories.

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.

A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery

2013 ◽  
Vol 451 (2) ◽  
pp. 313-328 ◽  
Author(s):  
Yinghong Gao ◽  
Stephen P. Davies ◽  
Martin Augustin ◽  
Anna Woodward ◽  
Umesh A. Patel ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Drug Discovery ◽  
Small Molecules ◽  
Chemical Structure ◽  
Rational Design ◽  
Kinase Inhibitors ◽  
Biochemical Assays ◽  
Potential Applications ◽  
Specific Inhibitors ◽  
Target Effects

Despite the development of a number of efficacious kinase inhibitors, the strategies for rational design of these compounds have been limited by target promiscuity. In an effort to better understand the nature of kinase inhibition across the kinome, especially as it relates to off-target effects, we screened a well-defined collection of kinase inhibitors using biochemical assays for inhibitory activity against 234 active human kinases and kinase complexes, representing all branches of the kinome tree. For our study we employed 158 small molecules initially identified in the literature as potent and specific inhibitors of kinases important as therapeutic targets and/or signal transduction regulators. Hierarchical clustering of these benchmark kinase inhibitors on the basis of their kinome activity profiles illustrates how they relate to chemical structure similarities and provides new insights into inhibitor specificity and potential applications for probing new targets. Using this broad dataset, we provide a framework for assessing polypharmacology. We not only discover likely off-target inhibitor activities and recommend specific inhibitors for existing targets, but also identify potential new uses for known small molecules.

scholarly journals Efficient Refolding of Aggregation-prone Citrate Synthase by Polyol Osmolytes

2005 ◽  
Vol 280 (16) ◽  
pp. 15553-15560 ◽  
Author(s):  
Rajesh Mishra ◽  
Robert Seckler ◽  
Rajiv Bhat
Keyword(s):  
Small Molecules ◽  
Molecular Chaperones ◽  
Rational Design ◽  
Protein Production ◽  
Citrate Synthase ◽  
Protein A ◽  
Complete Recovery ◽  
Hydroxyl Groups ◽  
Native State

Efficient refolding of proteins and prevention of their aggregation during folding are of vital importance in recombinant protein production and in finding cures for several diseases. We have used citrate synthase (CS) as a model to understand the mechanism of aggregation during refolding and its prevention using several known structure-stabilizing cosolvent additives of the polyol series. Interestingly, no parallel correlation between the folding effect and the general stabilizing effect exerted by polyols was observed. Although increasing concentrations of polyols increased protein stability in general, the refolding yields for CS decreased at higher polyol concentrations, with erythritol reducing the folding yields at all concentrations tested. Among the various polyols used, glycerol was the most effective in enhancing the CS refolding yield, and a complete recovery of enzymatic activity was obtained at 7mglycerol and 10 μg/ml protein, a result superior to the action of the molecular chaperones GroEL and GroESin vitro. A good correlation between the refolding yields and the suppression of protein aggregation by glycerol was observed, with no aggregation detected at 7m. The polyols prevented the aggregation of CS depending on the number of hydroxyl groups in them. Stopped-flow fluorescence kinetics experiments suggested that polyols, including glycerol, act very early in the refolding process, as no fast and slow phases were detectable. The results conclusively demonstrate that both the thermodynamic and kinetic aspects are critical in the folding process and that all structure-stabilizing molecules need not always help in productive folding to the native state. These findings are important for the rational design of small molecules for efficient refolding of various aggregation-prone proteins of commercial and medical relevance.

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