scholarly journals In Silico Engineering of Proteins That Recognize Small Molecules

10.5772/28001 ◽  
2012 ◽  
Author(s):  
Sushil Kumar ◽  
Gabriel Demo ◽  
Jaroslav Koca ◽  
Michaela Wimmerova
Keyword(s):  
Small Molecules ◽  
In Silico

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 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 Plant Antimicrobial Peptides: State of the Art, In Silico Prediction and Perspectives in the Omics Era

2020 ◽  
Vol 14 ◽  
pp. 117793222095273 ◽  
Author(s):  
Carlos André dos Santos-Silva ◽  
Luisa Zupin ◽  
Marx Oliveira-Lima ◽  
Lívia Maria Batista Vilela ◽  
João Pacifico Bezerra-Neto ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Small Molecules ◽  
In Silico ◽  
State Of The Art ◽  
Environmental Stresses ◽  
Gene Duplications ◽  
In Silico Prediction ◽  
Sequence Alignments ◽  
Plant Families ◽  
Simple Sequence

Even before the perception or interaction with pathogens, plants rely on constitutively guardian molecules, often specific to tissue or stage, with further expression after contact with the pathogen. These guardians include small molecules as antimicrobial peptides (AMPs), generally cysteine-rich, functioning to prevent pathogen establishment. Some of these AMPs are shared among eukaryotes (eg, defensins and cyclotides), others are plant specific (eg, snakins), while some are specific to certain plant families (such as heveins). When compared with other organisms, plants tend to present a higher amount of AMP isoforms due to gene duplications or polyploidy, an occurrence possibly also associated with the sessile habit of plants, which prevents them from evading biotic and environmental stresses. Therefore, plants arise as a rich resource for new AMPs. As these molecules are difficult to retrieve from databases using simple sequence alignments, a description of their characteristics and in silico (bioinformatics) approaches used to retrieve them is provided, considering resources and databases available. The possibilities and applications based on tools versus database approaches are considerable and have been so far underestimated.

Cycloxygenase-2 (COX-2) - A Potential Target for Screening of Small Molecules as Radiation Countermeasure Agents: An In Silico Study

2013 ◽  
Vol 9 (1) ◽  
pp. 35-45
Author(s):  
Jayadev Joshi ◽  
Tapan K. Barik ◽  
Nitisha Shrivastava ◽  
Manali Dimri ◽  
Subhajit Ghosh ◽  
...  
Keyword(s):  
Small Molecules ◽  
In Silico ◽  
Potential Target ◽  
In Silico Study ◽  
Cox 2

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.

In silico prediction of brain and CSF permeation of small molecules using PLS regression models

2008 ◽  
Vol 43 (8) ◽  
pp. 1581-1592 ◽  
Author(s):  
Stefanie Bendels ◽  
Manfred Kansy ◽  
Björn Wagner ◽  
Jörg Huwyler
Keyword(s):  
Small Molecules ◽  
In Silico ◽  
Regression Models ◽  
Pls Regression ◽  
In Silico Prediction

In silico design of novel anticancer antibody mimetic molecules targeting HER2

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14149-14149
Author(s):  
H. Nakajima ◽  
S. Tanuma ◽  
I. Fujiwara ◽  
N. Mizuta ◽  
K. Sakaguchi
Keyword(s):  
Breast Cancer ◽  
Small Molecules ◽  
In Silico ◽  
Metastatic Potential ◽  
Breast Cancer Patients ◽  
Term Survival ◽  
Regulatory Molecule ◽  
Self Assembling ◽  
Binding Pockets

14149 Background: HER2 is a unique receptor molecule for which no ligand has been found and functions as a coreceptor to form homo-and hetero-dimers with other three HER (1, 3 and 4) family members. The dimerization results in the activation of HER tyrosine kinase. This, in turn, promotes the tyrosine phosphorylation of certain proteins, leading to the stimulation of cell proliferation, invasion, and antiapoptosis. The overexpression of HER2 in breast cancer correlates with increased tumor growth and metastatic potential, and thereby poor long-term survival for the patient. A monoclonal antibody against HER2, named trastuzumab, is approved for breast cancer patients, while pertuzumab is currently in phaseIIclinical trial. The two antibodies bind to different epitopes in the extracellular domains of HER2. Trastuzumab binding mainly mediates the antibody-dependent cytotoxicity (ADCC). On the other hand, pertuzumab binding directly inhibits HER2 dimerization with its partner receptors, blocking the growth signaling and inducing apoptosis. Furthermore, the unique binding pockets on HER2 for trastuzumab and pertuzumab have been resolved and provide the important target domains for creation of new anticancer drugs. Methods: Based on these mechanisms, we are trying to design and create both antibodies-mimetic molecules using our in silico methodologies COSMOS (Conversion to small molecules through optimized-peptide strategy) and SARM (Self-assembling regulatory molecule). We design HRAP (HER2 reactive peptide)- SARM and HRAP- SARM- FAB (Fc?-binding peptide). HRAP-SARM may bind to HER2 pertuzumab binding site and sterically interferes with HER2 dimerization and induces apoptosis. HRAP- SARM- FAB is expected to induce both ADCC and apoptosis. Results and Conclusion: In this presentation, we will show the preliminary results and functions of the Ab-mimetics, HRAP- SARM and HRAP- SARM- FAB on human breast cancer cells overexpressing HER2, as compared to those of trastuzumab and pertuzumab. Since those Ab-mimetics are small molecules and cheap, the successful results are sure to promise the revolutionary therapy for refractory breast cancer. No significant financial relationships to disclose.

scholarly journals From in Silico Discovery to Intracellular Activity: Targeting JNK–Protein Interactions with Small Molecules

2012 ◽  
Vol 3 (9) ◽  
pp. 721-725 ◽  
Author(s):  
Tamer S. Kaoud ◽  
Chunli Yan ◽  
Shreya Mitra ◽  
Chun-Chia Tseng ◽  
Jiney Jose ◽  
...  
Keyword(s):  
Small Molecules ◽  
Protein Interactions ◽  
In Silico ◽  
Intracellular Activity

scholarly journals Drug connectivity mapping and functional analysis reveals therapeutic small molecules that differentially modulate myelination

2020 ◽  
Author(s):  
F Pieropan ◽  
AD Rivera ◽  
G Williams ◽  
F Calzolari ◽  
AM Butt ◽  
...  
Keyword(s):  
Small Molecules ◽  
In Silico ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Transcriptional Profiling ◽  
Drug Repurposing ◽  
Oligodendrocyte Progenitor Cells ◽  
Regulatory Pathways ◽  
Myelin Repair

AbstractOligodendrocytes are the myelin forming cells of the central nervous system (CNS) and are generated from oligodendrocyte progenitor cells (OPCs). Disruption or loss of oligodendrocytes and myelin has devastating effects on CNS function and integrity, which occurs in diverse neurological disorders, including Multiple Sclerosis (MS), Alzheimer’s disease (AD) and neuropsychiatric disorders. Hence, there is a need to develop new therapies that promote oligodendrocyte regeneration and myelin repair. A promising approach is drug repurposing, but most agents have potentially contrasting biological actions depending on the cellular context and their dose-dependent effects on intracellular regulatory pathways. Here, we have used a combined drug connectivity systems biology and neurobiological approach to identify compounds that exert positive and negative effects on oligodendroglia, depending on concentration. Notably, LY294002, a potent inhibitor of PI3K/Akt signalling, was the most highly ranked small molecule for both pro- and anti-oligodendroglial effects. We validated these in silico findings in multiple in vivo and ex vivo neurobiological models and demonstrate that low and high doses of LY294002 have a profoundly bipartite effect on the generation of OPCs and their differentiation into myelinating oligodendrocytes. Finally, we employed transcriptional profiling and signalling pathway activity assays to determine cell-specific mechanisms of action of LY294002 on oligodendrocytes and resolve optimal in vivo conditions required to promote myelin repair. These results demonstrate the power of multifactorial neurobiological and in silico strategies in determining the therapeutic potential of small molecules in neurodegenerative disorders.One-sentence summaryDrug discovery and CNS myelination

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