天然有機化合物にもとづくNTG-活性辞書システムの開発

Abstract

本研究では，天然有機化合物を対象とした，環系骨格構造とその関連する生理活性を相互に検索することができる辞書システムNTGdic/BOC (NTG dictionary for Bioactive Organic Compounds)を開発した．NTG (Non-Terminal vertex Graph)として表される環系骨格構造に注目し，天然有機化合物データベースKNApSAcK familyに収録されている51247件の化合物の化学構造式を対象に，単純グラフ，頂点重み付きグラフなど5種類の異なるグラフ表現を用いて，延べ57867件のNTGを抽出するとともに，既知の140種類の生理活性との関連付けを行った．これらの結果は関係データベース(関係辞書)としてシステムに実装した．NTGdic/BOCでは，構造エディタを用いて作画入力したクエリ化合物の化学構造式から，利用者が指定するグラフ表現レベルでのNTGを自動的に抽出し，NTG-活性辞書を用いて，関連する生理活性を参照することができる．一方，生理活性からNTG骨格構造を検索することや，各々のNTGの由来化合物を参照することもできる．また，類似構造(または類似NTG)検索も利用可能である．

Figures

Figure 1.

 Examples of various N TGs.

Figure 2.

 Five expression levels of NTGs extracted from Caffeine.

Figure 3.

 A workflow to generate TFS from 2-methylbutane.

Figure 5.

 Top 10 most common tetracyclic NTG/SGs in the dictionary.

Figure 6.

 Top 10 most common pentacyclic NTG/SGs in the dictionary.

Figure 7.

 Top 10 most common decacyclic NTG/SGs in the dictionary.

Figure 8.

 The NTG/SG extracted from Evodiamine and the related NTGs which are simple-graph-isomorphic to it.

Figure 9.

 Basic structure of the NTG-activity dictionary system.

Figure 10.

 A screenshot of the NTGdic/BOC extracting an NTG of a specified graph expression level (simple graph expression level, NTG/SG, for this case) from the original structure. At the lower left of the window, NTG structures of a specified level (NTG/DG for this case) that are related to an NTG identical to the one extracted above are listed.

Figure 11.

 A screenshot of the system when searched for NTGs that are associated with a particular biological activity.

Figure 12.

 A screenshot of the system when searched for NTGs similar to the NTG of a specified graph expression level (simple graph expression level, NTG/SG, for this case) of a query.

Tables

Table 1.  Results of NTG analysis of natural compounds stored in KNApSAcK core database.

Number ofrings	Compound	NTG/SG	/VG	/EG	/CG	/DG
0	1732	-	-	-	-	-
1	3602	30	96	101	200	333
2	7318	248	737	972	1456	1950
3	11380	909	1571	2111	2534	3234
4	9451	1543	1952	2538	2720	3209
5	6786	1542	1736	2228	2313	2685
6	3843	1197	1268	1539	1573	1764
7	1973	725	738	828	834	919
8	1241	466	474	535	540	580
9	799	298	302	334	338	366
10	491	216	223	236	242	257
11	244	142	143	149	150	159
12	161	98	99	105	106	106
13	135	70	72	80	82	85
14	53	37	37	37	37	38
15	31	26	26	26	26	26
16	11	11	11	11	11	11
17	9	9	9	9	9	9
18	6	6	6	6	6	6
19	1	1	1	1	1	1
20	2	2	2	2	2	2
21	4	3	3	3	3	3
24	1	1	1	1	1	1
Total	49274	7580	9507	11852	13184	15744

Table 2.  The number of NTGs related to biological activities.

-	Compound	NTG/SG	/VG	/EG	/CG	/DG
Annotated	4396 (8.9%)	2353 (31.0%)	2606 (27.4%)	2770 (23.4%)	2867 (21.7%)	2770 (17.6%)
Total	49274	7580	9507	11852	13184	15744

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