scholarly journals New computational studies to support cyclin-dependent kinase 9 inhibitor screening and design

2019 ◽  
Vol 89 (1) ◽  
pp. 31-38
Author(s):  
Márk Fábián ◽  
Balázs Balogh ◽  
Zsófia Czudor ◽  
László Őrfi
Keyword(s):  
Qsar Model ◽  
Regulation Of Transcription ◽  
Computational Studies ◽  
Cyclin Dependent Kinase ◽  
Active Compounds ◽  
Target Interaction ◽  
Antiapoptotic Proteins ◽  
Lead Selection ◽  
Pharmacophore Hypothesis ◽  
Selection Of

Aims: Cyclin-dependent kinase 9 (CDK9) plays a major role in the regulation of transcription. Its overexpression -which occurs in several types of cancer- increases the levels of certain antiapoptotic proteins that can lead to tumorigenesis, therefore the identification of new, more potent and more selective inhibitors is essential. Methods: In this study we present a computational approach, which can facilitate lead selection and optimization. Results: First, a pharmacophore hypothesis based on the active compounds has been developed to identify the key features for the ligand-target interaction. This was followed by the docking of the compounds into the active site of CDK9, the poses and interactions with the amino acids were compared with those of the co-crystallized ligand. The mode of their binding further explained the characteristics of these inhibitors while the docking scores can be a factor in the selection of active compounds in the future. Finally, a field-based QSAR model was also created, to predict the activity of inhibitor candidates. Conclusion: With our current work we deepened our knowledge about the interactions between CDK9 and its inhibitors, which can contribute to the discovery of novel CDK9 inhibitors.

scholarly journals Robotic QM/MM-driven maturation of antibody combining sites

2016 ◽  
Vol 2 (10) ◽  
pp. e1501695 ◽  
Author(s):  
Ivan V. Smirnov ◽  
Andrey V. Golovin ◽  
Spyros D. Chatziefthimiou ◽  
Anastasiya V. Stepanova ◽  
Yingjie Peng ◽  
...  
Keyword(s):  
Immune Response ◽  
In Vitro Selection ◽  
Single Point ◽  
Combinatorial Libraries ◽  
Single Point Mutation ◽  
Wild Type ◽  
Selection Of ◽  
Maturation Function

In vitro selection of antibodies from large repertoires of immunoglobulin (Ig) combining sites using combinatorial libraries is a powerful tool, with great potential for generating in vivo scavengers for toxins. However, addition of a maturation function is necessary to enable these selected antibodies to more closely mimic the full mammalian immune response. We approached this goal using quantum mechanics/molecular mechanics (QM/MM) calculations to achieve maturation in silico. We preselected A17, an Ig template, from a naïve library for its ability to disarm a toxic pesticide related to organophosphorus nerve agents. Virtual screening of 167,538 robotically generated mutants identified an optimum single point mutation, which experimentally boosted wild-type Ig scavenger performance by 170-fold. We validated the QM/MM predictions via kinetic analysis and crystal structures of mutant apo-A17 and covalently modified Ig, thereby identifying the displacement of one water molecule by an arginine as delivering this catalysis.

Selection of RNA-binding peptides from combinatorial libraries

1996 ◽  
Vol 26 (3-5) ◽  
pp. 258-258
Author(s):  
Kazuo Harada ◽  
Shelley Martin ◽  
Alan D. Frankel
Keyword(s):  
Rna Binding ◽  
Combinatorial Libraries ◽  
Binding Peptides ◽  
Selection Of

scholarly journals The Acceptability of Tempeh Based Sausage Formulations with Natural Preservatives Addition

2021 ◽  
Vol 13 (1) ◽  
pp. 10-22
Author(s):  
Nathasa Sihite
Keyword(s):  
Shelf Life ◽  
Food Products ◽  
Active Compounds ◽  
Flower Extract ◽  
Basic Taste ◽  
Randomized Design ◽  
Completely Randomized Design ◽  
Natural Preservatives ◽  
Harmful Effects ◽  
Selection Of

Sausage is a popular food for both children and adults. The main problem in sausage processing is their short shelf life. Synthetic preservatives such as nitrites are often added to sausage dough to extend the shelf life of sausages. Preservatives such as nitrites, if consumed too often can have harmful effects on health. The content of active compounds found in jasmine flowers is expected to be used as a source of natural preservatives in the processing of tempeh sausage in this study. This study aims to determine the acceptability of sausage formulations with the addition of natural preservatives. This study consisted of 3 treatments, namely tempeh sausage with extract variations of 0%, 0.1%, and 0.25%. This study used a completely randomized design (CRD). The concentration of jasmine flower extract had a significantly different effect on the taste of tempeh (p <0.05), where the higher the concentration of jasmine flower extract added to the tempeh sausage, the panelists' preference for the taste of the tempeh sausage would decrease. This is because the two basic ingredients of sausage, namely tempeh and jasmine flowers, already have a specific basic taste. The selection of preservatives made from natural ingredients can be a choice in developing food products, to minimize the use of synthetic preservatives in food products that are carcinogenic. Keywords: Sausage, tempeh, preservatives

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