• Title/Summary/Keyword: GNF

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Identification and Pharmacological Analysis of High Efficacy Small Molecule Inhibitors of EGF-EGFR Interactions in Clinical Treatment of Non-Small Cell Lung Carcinoma: a Computational Approach

  • Gudala, Suresh;Khan, Uzma;Kanungo, Niteesh;Bandaru, Srinivas;Hussain, Tajamul;Parihar, MS;Nayarisseri, Anuraj;Mundluru, Hema Prasad
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8191-8196
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    • 2016
  • Inhibition of EGFR-EGF interactions forms an important therapeutic rationale in treatment of non-small cell lung carcinoma. Established inhibitors have been successful in reducing proliferative processes observed in NSCLC, however patients suffer serious side effects. Considering the narrow therapeutic window of present EGFR inhibitors, the present study centred on identifying high efficacy EGFR inhibitors through structure based virtual screening strategies. Established inhibitors - Afatinib, Dacomitinib, Erlotinib, Lapatinib, Rociletinib formed parent compounds to retrieve similar compounds by linear fingerprint based tanimoto search with a threshold of 90%. The compounds (parents and respective similars) were docked at the EGF binding cleft of EGFR. Patch dock supervised protein-protein interactions were established between EGF and ligand (query and similar) bound and free states of EGFR. Compounds ADS103317, AKOS024836912, AGN-PC-0MXVWT, GNF-Pf-3539, SCHEMBL15205939 were retrieved respectively similar to Afatinib, Dacomitinib, Erlotinib, Lapatinib, Rociletinib. Compound-AGN-PC-0MXVWT akin to Erlotinib showed highest affinity against EGFR amongst all the compounds (parent and similar) assessed in the study. Further, AGN-PC-0MXVWT brought about significant blocking of EGFR-EGF interactions in addition showed appreciable ADMET properties and pharmacophoric features. In the study, we report AGN-PC-0MXVWT to be an efficient and high efficacy inhibitor of EGFR-EGF interactions identified through computational approaches.

Efficient Optimization Method for Polynomial Selection (다항식 선택을 위한 효율적인 최적화 기법)

  • Kim, Suhri;Kwon, Heetaek;Lee, Yongseong;Chang, Nam Su;Yoon, Kisoon;Kim, Chang Han;Park, Young-Ho;Hong, Seokhie
    • Journal of the Korea Institute of Information Security & Cryptology
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    • v.26 no.3
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    • pp.631-643
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    • 2016
  • Currently, General Number Field Sieve(GNFS) is known as the most efficient way for factoring large numbers. CADO-NFS is an open software based on GNFS, that was used to factor RSA-704. Polynomial selection in CADO-NFS can be divided into two stages - polynomial selection, and optimization of selected polynomial. However, optimization of selected polynomial in CADO-NFS is an immense procedure which takes 90% of time in total polynomial selection. In this paper, we introduce modification of optimization stage in CADO-NFS. We implemented precomputation table and modified optimization algorithm to reduce redundant calculation for faster optimization. As a result, we select same polynomial as CADO-NFS, with approximately 40% decrease in time.

Molecular Cloning and Bioinformatic Analysis of SPATA4 Gene

  • Liu, Shang-Feng;Ai, Chao;Ge, Zhong-Qi;Liu, Hai-Luo;Liu, Bo-Wen;He, Shan;Wang, Zhao
    • BMB Reports
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    • v.38 no.6
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    • pp.739-747
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    • 2005
  • Full-length cDNA sequences of four novel SPATA4 genes in chimpanzee, cow, chicken and ascidian were identified by bioinformatic analysis using mouse or human SPATA4 cDNA fragment as electronic probe. All these genes have 6 exons and have similar protein molecular weight and do not localize in sex chromosome. The mouse SPATA4 sequence is identified as significantly changed in cryptorchidism, which shares no significant homology with any known protein in swissprot databases except for the homologous genes in various vertebrates. Our searching results showed that all SPATA4 proteins have a putative conserved domain DUF1042. The percentages of putative SPATA4 protein sequence identity ranging from 30% to 99%. The high similarity was also found in 1 kb promoter regions of human, mouse and rat SPATA4 gene. The similarities of the sequences upstream of SPATA4 promoter also have a high proportion. The results of searching SymAtlas (http://symatlas.gnf.org/SymAtlas/) showed that human SPATA4 has a high expression in testis, especially in testis interstitial, leydig cell, seminiferous tubule and germ cell. Mouse SPATA4 was observed exclusively in adult mouse testis and almost no signal was detected in other tissues. The pI values of the protein are negative, ranging from 9.44 to 10.15. The subcellular location of the protein is usually in the nucleus. And the signal peptide possibilities for SPATA4 are always zero. Using the SNPs data in NCBI, we found 33 SNPs in human SPATA4 gene genomic DNA region, with the distribution of 29 SNPs in the introns. CpG island searching gives the data about CpG island, which shows that the regions of the CpG island have a high similarity with each other, though the length of the CpG island is different from each other.This research is a fundamental work in the fields of the bioinformational analysis, and also put forward a new way for the bioinformatic analysis of other genes.