Computational Molecular Design & Detection

Presentation on theme: "Computational Molecular Design & Detection"— Presentation transcript:

1 Computational Molecular Design & Detection
Y. Jane Tseng Graduate institute of Biomedical Electronics and Bioinformatics, Department of Computer Science and Information Engineering, School of Pharmacy, National Taiwan University

2 Computational Molecular Design & Detection
New Drug Discovery Computational Chemistry Computational Toxicology Chem-informatics Bio- informatics Biomarker Discovery Spectrum Analysis Metabol-omics 我的專長在發展新的計算方法和工具來設計、辨認小分子結構用在新藥開發及鑑定臨床上有用的生物指標 1124 1127 175

3 THE LAB IS FOR SOMEONE….. 對資工在未來的生計產業 可扮演什麼角色…

4 MOLECULAR PATENT

5 $$$$$

6 Laboratory of Molecular Design (分子結構計算設計)
本實驗室的研究主軸，以小分子結構為中心，探討分子結構與活體、活性、毒性之關係 1124 1127 175

7 如何以computing power 取代 animal Power好奇的
THE LAB IS FOR SOMEONE….. 如何以computing power 取代 animal Power好奇的

8 Computational Molecular Design
“ Novel Preclinical Tools for Predictive ADME-Toxicology” University of New Mexico Chem 21 > 5, 000 70% Drop rate “ … 10% improvement … would lead to a $100 million saving per drug.” - FDA White Paper, 2004

9 Computational Molecular Screening
EU 2012 Regulatory rules change Alternative Measurement Caco-2 cell permeation coefficients, ‧ Intestinal cell permeation coefficients ‧ Blood-brain barrier partition coefficients ‧ Aqueous solubility ‧ Skin permeation ‧ Critical micelle concentration ‧ Human Oral Drug Absorption

10 Computational Toxicology
ADME prediction Structural toxicology 解救老鼠大作戰

11 Computational hERG Toxicity Classification Model Based on QSAR and Support Vector Machines - Skolnik Award Symposium , "The Marriage, or at Least Dating, of Molecular Simulation and Modeling with QSAR Analysis: Exploring Chemometric Methods” at American Chemistry Society National Meeting, Boston , August 24, 2010

12 DESIGN

13 Lipoxygenase inhibition
Anti-VEGFR2/VEGFR 3, Anti-VEGFR2+ Anti-VEGFR 3 Kinase ABL inhibition Thromboxane receptor / synthase inhibition

14 利用LeadOp技術進行G9a抑制劑之設計
準備預先嵌合之分子片段資料庫 預測已知抑制物(UNC0646) 於G9a結合位之結合情形 將結合之UNC0646拆解為片段 評估各個片段是否需被替換 在預先嵌合之分子片段資料庫中找尋適合之片段 將新的片段和保留的片段進行連接 連接後的分子列表即為所設計之分子 Publications: J. Chem. Inf. Model. (2011), 51:7, Patent Application: In progress Technology Transfer: NA NSC 計畫編號：NSC B NRPB 計畫編號：100CAP1011-1 計畫主持人： 曾宇鳳 繳交日期：100年度第四季 14

15 THE LAB IS FOR SOMEONE….. 以前在醫科和資工中猶豫不決

16 MOLECULAR DETECTION

17 Metabolomics 發展應用新的代謝體之化學結構光譜比對與生物資訊方法找尋臨床上用來做為診斷、病程及癒後生物指標之結構及新藥設計。

18 Nature 2020 Vision For Nature's first issue of the new decade, Nature asked a selection of leading researchers and policy-makers where their fields will be ten years from now. Metabolomics is one out of 14 fields considered in Nature's 2020 vision. Other fields in Nature's 2020 vision in which metabolomics plays/can play a major role are 'Personalized Medicine', 'Microbiome', 'Drug Discovery', and 'Mental Health'.

19 Systems Biology and the rise of the “-omes”
Genomics Transcriptomics Proteomics Metabonomics Genomics - study of genes Transcriptomics -All the mRNA in a cell/tissue/organism Proteomics - All the proteins in a cell/tissue/organism Metabonomics/Metabolomics All the metabolites in a cell/tissue/organism NTU Metabolomics Group

20 代謝體核心實驗室

21 Services provided by NTU metacore
GC-MS GC-MS LC-QTOF

22 Data Intensive Pathway elucidation Spectrum Cross Validation
Statistical Experimental Design Correlation Spectrum Differential Spectrum (SED), Principal Component Analysis (PCA), Partial least-squares (PLS), Orthogonal-PLS (OPLS), and dynamic extensions thereof. This is illustrated by examples from the literature. NTU Metabolomics Group

23 NTU Metabolomics Group

24 MetaPick - A denoising and peak picking algorithm for LC/MS
1) EICs for the target m/z 2)Peak table of the sample Background subtraction Peak picking m/z RT intensity … 152.04 4.85 10000 NTU Center of Genomic Medicine No peak shape presumption Lower false positive Tsung-Jung Ho, Yeu-Chern Harn, Ching-Hua Kuo, Yufeng J. Tseng*, “MetaPick, a denoising and peak picking algorithm for extracting single compound from complex mixtures in liquid chromatography/mass spectrometry (LC/MS) metabolomics data”, 7th Annual Metabolomics Society Conference, Carins, Queensland, Australia, June, Best Informatics Poster Presentation Prize

25 Welcome! Room 529