In silico identification of new candidate genes for hereditary congenital facial paresis

2011 ◽  
Vol 29 (4) ◽  
pp. 451-460 ◽  
Author(s):  
Laura Tomás‐Roca ◽  
Antonio Pérez‐Aytés ◽  
Luis Puelles ◽  
Faustino Marín
Keyword(s):  
Candidate Genes ◽  
In Silico ◽  
Facial Paresis ◽  
In Silico Identification

In-Silico Identification of Drug Lead Molecule Against Pesticide Exposed-neurodevelopmental Disorders Through Network-Based Computational Model Approach

2019 ◽  
Vol 14 (5) ◽  
pp. 460-467 ◽  
Author(s):  
Neha Srivastava ◽  
Bhartendu Nath Mishra ◽  
Prachi Srivastava
Keyword(s):  
Binding Energy ◽  
Candidate Genes ◽  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
In Silico ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Drug Candidate ◽  
Potential Drug ◽  
In Silico Identification

Background: Neurodevelopmental Disorders (NDDs) are impairment of the growth and development of the brain or central nervous system, which occurs at the developmental stage. This can include developmental brain dysfunction, which can manifest as neuropsychiatric problems or impaired motor function, learning, language or non-verbal communication. These include the array of disorder, including: Autism Spectrum Disorders (ASD), Attention Deficit Hyperactivity Disorders (ADHD) etc. There is no particular diagnosis and cure for NDDs. These disorders seem to be result from a combination of genetic, biological, psychosocial and environmental risk factors. Diverse scientific literature reveals the adverse effect of environmental factors specifically, exposure of pesticides, which leads to growing number of human pathological conditions; among these, neurodevelopmental disorder is an emerging issue nowadays. Objective: The current study focused on in silico identification of potential drug targets for pesticides induced neurodevelopmental disorder including Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) and to design potential drug molecule for the target through drug discovery approaches. Methods: We identified 139 candidate genes for ADHD and 206 candidate genes for ASD from the NCBI database for detailed study. Protein-protein interaction network analysis was performed to identify key genes/proteins in the network by using STRING 10.0 database and Cytoscape 3.3.0 software. The 3D structure of target protein was built and validated. Molecular docking was performed against twenty seven possible phytochemicals i.e. beta amyrin, ajmaline, serpentine, urosolic, huperzine A etc. having neuroprotective activity. The best-docked compound was identified by the lowest Binding Energy (BE). Further, the prediction of drug-likeness and bioactivity analysis of leads were performed by using molinspiration cheminformatics software. Result & Conclusion: Based on betweenness centrality and node degree as a network topological parameter, solute carrier family 6 member 4 (SLC6A4) was identified as a common key protein in both the networks. 3-D structure of SLC6A4 protein was designed and validated respectively. Based on the lowest binding energy, beta amyrin (B.E = -8.54 kcal/mol) was selected as a potential drug candidate against SLC6A4 protein. Prediction of drug-likeness and bioactivity analysis of leads showed drug candidate as a potential inhibitor. Beta amyrin (CID: 73145) was obtained as the most potential therapeutic inhibitor for ASD & ADHD in human.

scholarly journals Syndrome to gene (S2G): in-silico identification of candidate genes for human diseases

2010 ◽  
Vol 31 (3) ◽  
pp. 229-236 ◽  
Author(s):  
Avitan Gefen ◽  
Raphael Cohen ◽  
Ohad S. Birk
Keyword(s):  
Candidate Genes ◽  
In Silico ◽  
Human Diseases ◽  
In Silico Identification

In Silico Identification and Molecular Characterization of Extracellular Cathepsin L Proteases from Giardia duodenalis

2020 ◽  
Vol 17 (4) ◽  
pp. 342-351
Author(s):  
Sergio A. Durán-Pérez ◽  
José G. Rendón-Maldonado ◽  
Lucio de Jesús Hernandez-Diaz ◽  
Annete I. Apodaca-Medina ◽  
Maribel Jiménez-Edeza ◽  
...  
Keyword(s):  
In Silico ◽  
Cathepsin L ◽  
Three Dimensional ◽  
Giardia Duodenalis ◽  
Evolutionary Genetics ◽  
Extracellular Proteins ◽  
In Silico Identification ◽  
Dimensional Models ◽  
Three Dimensional Models

Background: The protozoan Giardia duodenalis, which causes giardiasis, is an intestinal parasite that commonly affects humans, mainly pre-school children. Although there are asymptomatic cases, the main clinical features are chronic and acute diarrhea, nausea, abdominal pain, and malabsorption syndrome. Little is currently known about the virulence of the parasite, but some cases of chronic gastrointestinal alterations post-infection have been reported even when the infection was asymptomatic, suggesting that the cathepsin L proteases of the parasite may be involved in the damage at the level of the gastrointestinal mucosa. Objective: The aim of this study was the in silico identification and characterization of extracellular cathepsin L proteases in the proteome of G. duodenalis. Methods: The NP_001903 sequence of cathepsin L protease from Homo sapienswas searched against the Giardia duodenalisproteome. The subcellular localization of Giardia duodenaliscathepsin L proteases was performed in the DeepLoc-1.0 server. The construction of a phylogenetic tree of the extracellular proteins was carried out using the Molecular Evolutionary Genetics Analysis software (MEGA X). The Robetta server was used for the construction of the three-dimensional models. The search for possible inhibitors of the extracellular cathepsin L proteases of Giardia duodenaliswas performed by entering the three-dimensional structures in the FINDSITEcomb drug discovery tool. Results: Based on the amino acid sequence of cathepsin L from Homo sapiens, 8 protein sequences were identified that have in their modular structure the Pept_C1A domain characteristic of cathepsins and two of these proteins (XP_001704423 and XP_001704424) are located extracellularly. Threedimensional models were designed for both extracellular proteins and several inhibitory ligands with a score greater than 0.9 were identified. In vitrostudies are required to corroborate if these two extracellular proteins play a role in the virulence of Giardia duodenalisand to discover ligands that may be useful as therapeutic targets that interfere in the mechanism of pathogenesis generated by the parasite. Conclusion: In silicoanalysis identified two proteins in the Giardia duodenalisprotein repertoire whose characteristics allowed them to be classified as cathepsin L proteases, which may be secreted into the extracellular medium to act as virulence factors. Three-dimensional models of both proteins allowed the identification of inhibitory ligands with a high score. The results suggest that administration of those compounds might be used to block the endopeptidase activity of the extracellular cathepsin L proteases, interfering with the mechanisms of pathogenesis of the protozoan parasite Giardia duodenalis.

In silico identification of novel small molecule umami peptide from ovotransferrin

2021 ◽  
Author(s):  
Wenzhu Zhao ◽  
Jingbo He ◽  
Zhipeng Yu ◽  
Sijia Wu ◽  
Jianrong Li ◽  
...  
Keyword(s):  
Small Molecule ◽  
In Silico ◽  
In Silico Identification
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