• Title, Summary, Keyword: virtual screening

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Evaluation of Advanced Structure-Based Virtual Screening Methods for Computer-Aided Drug Discovery

  • Lee, Hui-Sun;Choi, Ji-Won;Yoon, Suk-Joon
    • Genomics & Informatics
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    • v.5 no.1
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    • pp.24-29
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    • 2007
  • Computational virtual screening has become an essential platform of drug discovery for the efficient identification of active candidates. Moleculardocking, a key technology of receptor-centric virtual screening, is commonly used to predict the binding affinities of chemical compounds on target receptors. Despite the advancement and extensive application of these methods, substantial improvement is still required to increase their accuracy and time-efficiency. Here, we evaluate several advanced structure-based virtual screening approaches for elucidating the rank-order activity of chemical libraries, and the quantitative structureactivity relationship (QSAR). Our results show that the ensemble-average free energy estimation, including implicit solvation energy terms, significantly improves the hit enrichment of the virtual screening. We also demonstrate that the assignment of quantum mechanical-polarized (QM-polarized) partial charges to docked ligands contributes to the reproduction of the crystal pose of ligands in the docking and scoring procedure.

DVSF: A Distributed System for Virtual Screening (DVSF: 가상 검색을 위한 분산 시스템)

  • 황석찬;최종선;이상근;임재훈;최재영;노경태;이지수
    • Journal of KIISE:Computing Practices and Letters
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    • v.9 no.1
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    • pp.25-32
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    • 2003
  • As one of a new generation of industries, biotechnology is currently spotlighted, and is creating new research and industrial areas that can be readily combined with information technology. Among them, virtual screening is a method for new drug design which uses computer simulation to virtually design active drug candidates for special disease. In this paper, we present a distributed system for virtual screening, called DVSF(Distributed Virtual Screening Facilities). DVSF is designed and developed to perform virtual screening efficiently on logically distributed idle or strategic resources in a small or medium scale laboratory.

The Trend of e-Science Projects for Virtual Screening (Virtual Screening을 위한 e-Science 프로젝트 동향)

  • KIM, Nam Gyu;AHN, Sun Il;LEE, Sehoon;LEE, June H.;HWANG, Soon Wook
    • Proceedings of the Korea Contents Association Conference
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    • pp.569-573
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    • 2007
  • e-Science is a new paradigm to increase the research efficiency by applying the state-of-the-art information technology to the classical research methodology. Among the research fields influenced by e-Science, Biology and Bioinformatics are the fields that are using IT very actively. And virtual screening, a procedure for the drug discovery, is one of the bioinformatics applications which requires a large amount of computing resources. In this paper, WISDOM, which is a e-Science project to design a new drug for Malaria and Avian flu, and related projects are introduced and the joint research between KISTI and Chun-nam university planned for the virtual screening research is explained.

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Design and Implementation of Service based Virtual Screening System in Grids (그리드에서 서비스 기반 가상 탐색 시스템 설계 및 구현)

  • Lee, Hwa-Min;Chin, Sung-Ho;Lee, Jong-Hyuk;Lee, Dae-Won;Park, Seong-Bin;Yu, Heon-Chang
    • Journal of KIISE:Computer Systems and Theory
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    • v.35 no.6
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    • pp.237-247
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    • 2008
  • A virtual screening is the process of reducing an unmanageable number of compounds to a limited number of compounds for the target of interest by means of computational techniques such as molecular docking. And it is one of a large-scale scientific application that requires large computing power and data storage capability. Previous applications or softwares for molecular docking such as AutoDock, FlexX, Glide, DOCK, LigandFit, ViSION were developed to be run on a supercomputer, a workstation, or a cluster-computer. However the virtual screening using a supercomputer has a problem that a supercomputer is very expensive and the virtual screening using a workstation or a cluster-computer requires a long execution time. Thus we propose a service-based virtual screening system using Grid computing technology which supports a large data intensive operation. We constructed 3-dimensional chemical molecular database for virtual screening. And we designed a resource broker and a data broker for supporting efficient molecular docking service and proposed various services for virtual screening. We implemented service based virtual screening system with DOCK 5.0 and Globus 3.2 toolkit. Our system can reduce a timeline and cost of drug or new material design.

Toward the Virtual Screening of α-Glucosidase Inhibitors with the Homology-Modeled Protein Structure

  • Park, Jung-Hum;Ko, Sung-Min;Park, Hwang-Seo
    • Bulletin of the Korean Chemical Society
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    • v.29 no.5
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    • pp.921-927
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    • 2008
  • Discovery of $\alpha$-glucosidase inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of diabetes and the other carbohydrate mediated diseases. As a method for the discovery of new novel inhibitors of $\alpha$-glucosidase, we have addressed the performance of the computer-aided drug design protocol involving the homology modeling of $\alpha$-glucosidase and the structure-based virtual screening with the two docking tools: FlexX and the automated and improved AutoDock implementing the effects of ligand solvation in the scoring function. The homology modeling of $\alpha$-glucosidase from baker’s yeast provides a high-quality 3-D structure enabling the structure-based inhibitor design. Of the two docking programs under consideration, AutoDock is found to be more accurate than FlexX in terms of scoring putative ligands to the extent of 5-fold enhancement of hit rate in database screening when 1% of database coverage is used as a cutoff. A detailed binding mode analysis of the known inhibitors shows that they can be stabilized in the active site of $\alpha$- glucosidase through the simultaneous establishment of the multiple hydrogen bond and hydrophobic interactions. The present study demonstrates the usefulness of the automated AutoDock program with the improved scoring function as a docking tool for virtual screening of new $\alpha$-glucosidase inhibitors as well as for binding mode analysis to elucidate the activities of known inhibitors.

Discovery of Novel DUSP4 Inhibitors through the Virtual Screening with Docking Simulations

  • Park, Hwangseo;Jeon, Tae Jin;Chien, Pham Ngoc;Park, So Ya;Oh, Sung Min;Kim, Seung Jun;Ryu, Seong Eon
    • Bulletin of the Korean Chemical Society
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    • v.35 no.9
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    • pp.2655-2659
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    • 2014
  • Dual specificity protein phosphatase 4 (DUSP4) has been considered a promising target for the development of therapeutics for various human cancers. Here, we report the first example for a successful application of the structure-based virtual screening to identify the novel small-molecule DUSP4 inhibitors. As a consequence of the virtual screening with the modified scoring function to include an effective molecular solvation free energy term, five micromolar DUSP4 inhibitors are found with the associated $IC_{50}$ values ranging from 3.5 to $10.8{\mu}M$. Because these newly identified inhibitors were also screened for having desirable physicochemical properties as a drug candidate, they may serve as a starting point of the structure-activity relationship study to optimize the medical efficacy. Structural features relevant to the stabilization of the new inhibitors in the active site of DUSP4 are discussed in detail.