第三章 結果與討論
3.2 討論
統計在 5 個目標蛋白質上的實驗結果，總共識別了 27 個作用力類型錨點，
其中有 22 個錨點(82%)與現有受質結合有關，錨點周圍的殘基共有 53 個，經由 Consurf 計分在 7 至 9 分，也就是在演化上有高度保存性的殘基有 52 個(98%)，
製成圖表如圖 二十一以及圖 二十二。
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圖 二十一 錨點參與受質結合統計圖表。x 軸為 5 個目標蛋白質，y 軸為在目標蛋白質上，參與 受質結合的錨點數與所有錨點數的百分比例，以 TK 為例，識別出總共 7 個錨點，其中有 5 個錨 點與受質結合有關，比例大約是 71%。
圖 二十二 錨點周圍殘基 Consurf 分數圖表。x 軸為各目標蛋白質所識別出的錨點周圍殘基，y 軸為經由 Consurf 網站所計算的殘基在演化上保存分數，從 1-9 分，在 7 分以上(圖中以紅線標示) 的殘基被認為具有高度保存性。
上述結果顯示，透過利用官能基嵌合所識別的作用力類型錨點，常常位於蛋 白質與配體結合區域中的關鍵交互作用區，推測這些錨點在生物體內生化反應中 扮演重要的角色。我們相信以官能基為基礎之區域官能基地圖將能應用在藥物發
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展、藥物最佳化以及幫助相關研究者快速地了解蛋白質與配體間交互作用之機 制。
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附錄一 名詞中英對照
蛋白質與配體間交互作用 protein-ligand interaction
界面 interface
結合區域 binding site
官能基 moiety
殘基 residue
前導化合物 lead compound
虛擬藥物篩選 virtual screening
分子嵌合 molecular docking
計分方程式 scoring function
親和力 affinity
篩選後分析 post-screening analysis 實驗驗證 experimental verification 區域官能基地圖 Site-Moiety Map, SiMMap
交互作用剖繪 interaction profile
受質 substrate
催化反應殘基 catalytic residue
多重序列比對 multiple sequence alignment, MSA
活化區 active site
胺基酸 amino acid
激酶抑制劑 kinase inhibitor
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附錄二 FDA 驗證藥物其官能基組成
統計 34 個官能基在 1382 個 FDA 認證藥物中出現情形，礙於篇幅只列出 100 個分子量在 650 以下並且官能基出現次數較多的 FDA 認證藥物列表。欄位由左 至右分別為 FDA 驗證藥物結構、FDA 驗證藥物名稱以及出現在該藥物上的官能 結構。
FDA 驗證
藥物結構 FDA 驗證藥物名稱 官能基結構
adefovir_dipivoxil
aliskiren
amiodarone
amprenavir
44
arbutamine
aspartame
bacampicillin
bambuterol
benazepril
benzonatate
45
bepotastine
bepridil
betaxolol
bevantolol
bisoprolol
46
bosentan
buprenorphine
candoxatril
carbinoxamine
carvedilol
cefpiramide
47
cephaloglycin
cilazapril
cyclopentolate
darunavir
deserpidine
dicyclomine
48
diltiazem
dipivefrin
dobutamine
doxylamine
droxidopa
49
enalapril
epinephrine
ergoloid_mesylate
esmolol
fosamprenavir
fosinopril
50
gadobenate_dimeglumine
gallamine_triethiodide
gemfibrozil
hexylcaine
hydrocortamate
51
indinavir
isoetharine
isoproterenol
labetalol
lapatinib
latamoxef
52
latanoprost
lepirudin
lercanidipine
leuprolide
leuprolide_acetate
53
levomethadyl_acetate
lopinavir
methadyl_acetate
metipranolol
metoprolol
moexipril
54
nelfinavir
novobiocin
oseltamivir
oxprenolol
oxybuprocaine
55
oxybutynin
oxyphencyclimine
penbutolol
perindopril
pivampicillin
proparacaine
56
propoxyphene
quinapril
ramipril
remifentanil
remikiren
57
repaglinide
rescinnamine
reserpine
rosiglitazone
rosuvastatin
salbutamol
58
salmeterol
silodosin
spirapril
streptomycin
tamsulosin
59
terbutaline
tirofiban
tramadol
trandolapril
travoprost
trimethobenzamide
60
trimetrexate
valaciclovir
valganciclovir
valsartan
venlafaxine
61
verapamil
ximelagatran