scholarly journals Template Instrumentation for "Accurate Constant via Transient Incomplete Separation" (ACTIS)

2021 ◽  
Author(s):  
Jean-Luc Rukundo ◽  
Sven Kochmann ◽  
Tong Ye Wang ◽  
Nikita A. Ivanov ◽  
J.C. Yves Le Blanc ◽  
...  
Keyword(s):  
Small Molecule ◽  
In Silico ◽  
Diffusion Processes ◽  
Equilibrium Dissociation Constant ◽  
Transverse Diffusion ◽  
Advection Diffusion ◽  
In Silico Studies ◽  
Equilibrium Dissociation ◽  
Pressure Driven Flow ◽  
System Geometry

<p>ACTIS is a new method for finding the equilibrium dissociation constant <i>K</i><sub>d</sub> of a protein–small molecule complex based on transient incomplete separation of the complex from the unbound small molecule in a capillary. This separation is caused by differential transverse diffusion of the complex and the small molecule in a pressure-driven flow. The advection-diffusion processes underlying ACTIS can be described by a system of partial differential equations allowing for a virtual ACTIS instrument to be built and ACTIS to be studied in silico. The previous in-silico studies show that large variations in the fluidic system geometry do not affect the accuracy of <i>K</i><sub>d</sub> determination, thus, proving that ACTIS is conceptually accurate. The conceptual accuracy does not preclude, however, instrumental inaccuracy caused by run-to-run signal drifts. Here we report on assembling a physical ACTIS instrument with a fluidic system that mimics the virtual one and proving the absence of signal drifts. Furthermore, we confirmed method ruggedness by assembling a second ACTIS instrument and comparing the results of experiments performed with both instruments in parallel. Despite some differences between the instruments and, accordingly, significant differences in their respective separagrams, we found that the <i>K</i><sub>d</sub> values determined for identical samples with these instruments were equal. Conclusively, the fluidic system presented here can serve as a template for reliable ACTIS instrumentation.</p>

scholarly journals Template Instrumentation for "Accurate Constant via Transient Incomplete Separation" (ACTIS)

2021 ◽  
Author(s):  
Jean-Luc Rukundo ◽  
Sven Kochmann ◽  
Tong Ye Wang ◽  
Nikita A. Ivanov ◽  
J.C. Yves Le Blanc ◽  
...  
Keyword(s):  
Small Molecule ◽  
In Silico ◽  
Diffusion Processes ◽  
Equilibrium Dissociation Constant ◽  
Transverse Diffusion ◽  
Advection Diffusion ◽  
In Silico Studies ◽  
Equilibrium Dissociation ◽  
Pressure Driven Flow ◽  
System Geometry

<p>ACTIS is a new method for finding the equilibrium dissociation constant <i>K</i><sub>d</sub> of a protein–small molecule complex based on transient incomplete separation of the complex from the unbound small molecule in a capillary. This separation is caused by differential transverse diffusion of the complex and the small molecule in a pressure-driven flow. The advection-diffusion processes underlying ACTIS can be described by a system of partial differential equations allowing for a virtual ACTIS instrument to be built and ACTIS to be studied in silico. The previous in-silico studies show that large variations in the fluidic system geometry do not affect the accuracy of <i>K</i><sub>d</sub> determination, thus, proving that ACTIS is conceptually accurate. The conceptual accuracy does not preclude, however, instrumental inaccuracy caused by run-to-run signal drifts. Here we report on assembling a physical ACTIS instrument with a fluidic system that mimics the virtual one and proving the absence of signal drifts. Furthermore, we confirmed method ruggedness by assembling a second ACTIS instrument and comparing the results of experiments performed with both instruments in parallel. Despite some differences between the instruments and, accordingly, significant differences in their respective separagrams, we found that the <i>K</i><sub>d</sub> values determined for identical samples with these instruments were equal. Conclusively, the fluidic system presented here can serve as a template for reliable ACTIS instrumentation.</p>

scholarly journals Nature as a Treasure Trove for Anti-COVID-19: Luteolin and Naringenin from Indonesian Traditional Herbal Medicine Reveal Potential SARS-CoV-2 Mpro Inhibitors Insight from in Silico Studies

2020 ◽  
Author(s):  
Wahyu Prasetyo ◽  
Triana Kusumaningsih ◽  
Maulidan Firdaus
Keyword(s):  
Chinese Medicine ◽  
Herbal Medicine ◽  
Traditional Chinese Medicine ◽  
Medicinal Plants ◽  
Small Molecule ◽  
In Silico ◽  
Dft Studies ◽  
Traditional Herbal Medicine ◽  
In Silico Studies ◽  
Bioactive Phytochemicals

<div>Since the worldwide is currently facing the COVID-19 pandemic, there are no drugs or vaccines have been approved</div><div>for the treatment of SARS-CoV-2 infection. Therefore, there is an urgent need for in-depth research on emerging</div><div>human infectious coronaviruses. As part of our endeavour in combating this COVID-19 pandemic, in this paper, we</div><div>report on the discovery of an active antiviral small-molecule from Indonesian traditional herbal medicine used in Jamu</div><div>to inhibit 3CLpro of SARS-CoV-2 using in-silico approaches. As one of the mega biodiversity countries, Indonesia has</div><div>more than 1,180 species that can be prospected for medicine plants. Jamu, the Indonesian traditional herbal medicine,</div><div>is supposed to have similar potentials as those of traditional Chinese medicine (TCM). However, due to the lack of</div><div>scientific proof, Jamu is not recognised in the Guideline of COVID-19 Patients, particularly in Indonesia. Thus, in</div><div>this study, we performed virtual docking screening along with pharmacokinetic and DFT studies of selected 49</div><div>bioactive phytochemicals from several medicinal plants used in Jamu against the 3CLpro enzyme of SARS-CoV-2.</div><div>From the result, it was noted that from a set of 49 phytochemicals of medicinal plants used in Jamu, 2 phytochemicals,</div><div>i.e., Luteolin and Naringenin were identified as potential druggable inhibitors candidates of 3CLpro of SARS CoV-2.</div>

scholarly journals Accurate Kd via Transient Incomplete Separation

2019 ◽  
Author(s):  
Nicolas Sisavath ◽  
Jean Luc Rukundo ◽  
J.C. Yves Le Blanc ◽  
Victor A. Galievsky ◽  
Jiayin Bao ◽  
...  
Keyword(s):  
Computer Simulation ◽  
Dissociation Constant ◽  
Small Molecule ◽  
Equilibrium Dissociation Constant ◽  
Practical Application ◽  
Constant Concentration ◽  
Binding Isotherm ◽  
Equilibrium Dissociation

<div>Current methods for finding the equilibrium dissociation constant, <i>K</i><sub>d</sub>, of protein-small molecule complexes have inherent sources of inaccuracy.</div><div><br></div><div>We introduce “Accurate <i>K</i><sub>d</sub> via Transient Incomplete Separation” (AKTIS), an approach that is free of known sources of inaccuracy. Conceptually, in AKTIS, a short plug of the pre-equilibrated protein-small molecule mixture is pressure-propagated in a capillary, causing transient incomplete separation of the complex from the unbound small molecule. A superposition of signals from these two components is measured near the capillary exit as a function of time, for different concentrations of the protein and a constant concentration of the small molecule. Finally, a classical binding isotherm is built and used to find accurate <i>K</i><sub>d</sub> value. <br></div><div><br></div><div>Here we prove AKTIS validity theoretically and by computer simulation, present a fluidic system satisfying AKTIS requirements, and demonstrate practical application of AKTIS to finding <i>K</i><sub>d</sub> of protein-small molecule complexes.</div>

Accurate Kd via Transient Incomplete Separation

2019 ◽  
Author(s):  
Nicolas Sisavath ◽  
Jean Luc Rukundo ◽  
J.C. Yves Le Blanc ◽  
Victor A. Galievsky ◽  
Jiayin Bao ◽  
...  
Keyword(s):  
Computer Simulation ◽  
Dissociation Constant ◽  
Small Molecule ◽  
Equilibrium Dissociation Constant ◽  
Practical Application ◽  
Constant Concentration ◽  
Binding Isotherm ◽  
Equilibrium Dissociation

<div>Current methods for finding the equilibrium dissociation constant, <i>K</i><sub>d</sub>, of protein-small molecule complexes have inherent sources of inaccuracy.</div><div><br></div><div>We introduce “Accurate <i>K</i><sub>d</sub> via Transient Incomplete Separation” (AKTIS), an approach that is free of known sources of inaccuracy. Conceptually, in AKTIS, a short plug of the pre-equilibrated protein-small molecule mixture is pressure-propagated in a capillary, causing transient incomplete separation of the complex from the unbound small molecule. A superposition of signals from these two components is measured near the capillary exit as a function of time, for different concentrations of the protein and a constant concentration of the small molecule. Finally, a classical binding isotherm is built and used to find accurate <i>K</i><sub>d</sub> value. <br></div><div><br></div><div>Here we prove AKTIS validity theoretically and by computer simulation, present a fluidic system satisfying AKTIS requirements, and demonstrate practical application of AKTIS to finding <i>K</i><sub>d</sub> of protein-small molecule complexes.</div>

Transient Incomplete Separation Facilitates Finding Accurate Equilibrium Dissociation Constant of Protein–Small Molecule Complex

2019 ◽  
Vol 131 (20) ◽  
pp. 6707-6711
Author(s):  
Nicolas Sisavath ◽  
Jean‐Luc Rukundo ◽  
J. C. Yves Le Blanc ◽  
Victor A. Galievsky ◽  
Jiayin Bao ◽  
...  
Keyword(s):  
Dissociation Constant ◽  
Small Molecule ◽  
Equilibrium Dissociation Constant ◽  
Equilibrium Dissociation

scholarly journals Nature as a Treasure Trove for Anti-COVID-19: Luteolin and Naringenin from Indonesian Traditional Herbal Medicine Reveal Potential SARS-CoV-2 Mpro Inhibitors Insight from in Silico Studies

2020 ◽  
Author(s):  
Wahyu Prasetyo ◽  
Triana Kusumaningsih ◽  
Maulidan Firdaus
Keyword(s):  
Chinese Medicine ◽  
Herbal Medicine ◽  
Traditional Chinese Medicine ◽  
Medicinal Plants ◽  
Small Molecule ◽  
In Silico ◽  
Dft Studies ◽  
Traditional Herbal Medicine ◽  
In Silico Studies ◽  
Bioactive Phytochemicals

<div>Since the worldwide is currently facing the COVID-19 pandemic, there are no drugs or vaccines have been approved</div><div>for the treatment of SARS-CoV-2 infection. Therefore, there is an urgent need for in-depth research on emerging</div><div>human infectious coronaviruses. As part of our endeavour in combating this COVID-19 pandemic, in this paper, we</div><div>report on the discovery of an active antiviral small-molecule from Indonesian traditional herbal medicine used in Jamu</div><div>to inhibit 3CLpro of SARS-CoV-2 using in-silico approaches. As one of the mega biodiversity countries, Indonesia has</div><div>more than 1,180 species that can be prospected for medicine plants. Jamu, the Indonesian traditional herbal medicine,</div><div>is supposed to have similar potentials as those of traditional Chinese medicine (TCM). However, due to the lack of</div><div>scientific proof, Jamu is not recognised in the Guideline of COVID-19 Patients, particularly in Indonesia. Thus, in</div><div>this study, we performed virtual docking screening along with pharmacokinetic and DFT studies of selected 49</div><div>bioactive phytochemicals from several medicinal plants used in Jamu against the 3CLpro enzyme of SARS-CoV-2.</div><div>From the result, it was noted that from a set of 49 phytochemicals of medicinal plants used in Jamu, 2 phytochemicals,</div><div>i.e., Luteolin and Naringenin were identified as potential druggable inhibitors candidates of 3CLpro of SARS CoV-2.</div>

Transient Incomplete Separation Facilitates Finding Accurate Equilibrium Dissociation Constant of Protein–Small Molecule Complex

2019 ◽  
Vol 58 (20) ◽  
pp. 6635-6639 ◽  
Author(s):  
Nicolas Sisavath ◽  
Jean‐Luc Rukundo ◽  
J. C. Yves Le Blanc ◽  
Victor A. Galievsky ◽  
Jiayin Bao ◽  
...  
Keyword(s):  
Dissociation Constant ◽  
Small Molecule ◽  
Equilibrium Dissociation Constant ◽  
Equilibrium Dissociation

scholarly journals Accurate Kd via Transient Incomplete Separation

2019 ◽  
Author(s):  
Nicolas Sisavath ◽  
Jean Luc Rukundo ◽  
J.C. Yves Le Blanc ◽  
Victor A. Galievsky ◽  
Jiayin Bao ◽  
...  
Keyword(s):  
Computer Simulation ◽  
Dissociation Constant ◽  
Small Molecule ◽  
Equilibrium Dissociation Constant ◽  
Practical Application ◽  
Constant Concentration ◽  
Binding Isotherm ◽  
Equilibrium Dissociation

<div>Current methods for finding the equilibrium dissociation constant, <i>K</i><sub>d</sub>, of protein-small molecule complexes have inherent sources of inaccuracy.</div><div><br></div><div>We introduce “Accurate <i>K</i><sub>d</sub> via Transient Incomplete Separation” (AKTIS), an approach that is free of known sources of inaccuracy. Conceptually, in AKTIS, a short plug of the pre-equilibrated protein-small molecule mixture is pressure-propagated in a capillary, causing transient incomplete separation of the complex from the unbound small molecule. A superposition of signals from these two components is measured near the capillary exit as a function of time, for different concentrations of the protein and a constant concentration of the small molecule. Finally, a classical binding isotherm is built and used to find accurate <i>K</i><sub>d</sub> value. <br></div><div><br></div><div>Here we prove AKTIS validity theoretically and by computer simulation, present a fluidic system satisfying AKTIS requirements, and demonstrate practical application of AKTIS to finding <i>K</i><sub>d</sub> of protein-small molecule complexes.</div>

Critical Review on the Chemical Aspects of Cannabidiol (CBD) and Harmonization of Computational Bioactivity Data

2020 ◽  
Vol 28 (2) ◽  
pp. 213-237 ◽  
Author(s):  
Andrea Mastinu ◽  
Giovanni Ribaudo ◽  
Alberto Ongaro ◽  
Sara Anna Bonini ◽  
Maurizio Memo ◽  
...  
Keyword(s):  
In Silico ◽  
Cannabis Sativa ◽  
Therapeutic Potential ◽  
The Novel ◽  
In Silico Studies ◽  
Computational Data ◽  
Synthetic Approaches ◽  
Analytical Approaches ◽  
Yield Sensitivity ◽  
Therapeutic Profile

: Cannabidiol (CBD) is a non-psychotropic phytocannabinoid which represents one of the constituents of the “phytocomplex” of Cannabis sativa. This natural compound is attracting growing interest since when CBD-based remedies and commercial products were marketed. This review aims to exhaustively address the extractive and analytical approaches that have been developed for the isolation and quantification of CBD. Recent updates on cutting-edge technologies were critically examined in terms of yield, sensitivity, flexibility and performances in general, and are reviewed alongside original representative results. As an add-on to currently available contributions in the literature, the evolution of the novel, efficient synthetic approaches for the preparation of CBD, a procedure which is appealing for the pharmaceutical industry, is also discussed. Moreover, with the increasing interest on the therapeutic potential of CBD and the limited understanding of the undergoing biochemical pathways, the reader will be updated about recent in silico studies on the molecular interactions of CBD towards several different targets attempting to fill this gap. Computational data retrieved from the literature have been integrated with novel in silico experiments, critically discussed to provide a comprehensive and updated overview on the undebatable potential of CBD and its therapeutic profile.

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