第七章.htm

这是一些经典算法的描述

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<h1 align=center style='text-align:center'><span style='font-family:隶书;
color:#EFCE8F'>第七章</span><span lang=EN-US style='font-size:36.0pt;mso-ascii-font-family:
隶书;mso-fareast-font-family:隶书;color:#EFCE8F'>&nbsp;</span><span
style='font-family:隶书;color:#EFCE8F'>蛋白质结构预测</span><span lang=EN-US><o:p></o:p></span></h1>

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<p><span lang=EN-US><SELECT NAME="str_sel"
onchange="javascript:window.location=(this.options[this.selectedIndex].value);">
<OPTION SELECTED>========= 选择章节 ==========
<OPTION VALUE="7.1.htm">7.1 引言
<OPTION VALUE="7.2.htm">7.2 蛋白质二级结构预测
<OPTION VALUE="7.3.htm">7.3 RNA二级结构的预测
<OPTION VALUE="7.4.htm">7.4 蛋白质空间结构预测
<OPTION VALUE="7.5.htm">7.5 蛋白质空间结构比较
<OPTION VALUE="7.question.htm">问题与练习
<OPTION VALUE="7.referance.htm">参考文献
</SELECT><o:p></o:p></span></p>

<p style='line-height:150%'><span lang=EN-US style='font-size:10.0pt;
mso-bidi-font-size:8.0pt;font-family:"Times New Roman"'>&nbsp;&nbsp;&nbsp; </span><span
style='font-size:10.0pt;mso-bidi-font-size:8.0pt;mso-ascii-font-family:"Times New Roman";
mso-hansi-font-family:"Times New Roman"'>一种生物体的基因组规定了所有构成该生物体的蛋白质，基因规定了组成蛋白质的氨基酸序列。虽然蛋白质由氨基酸的线性序列组成，但是，它们只有折叠成特定的空间构象才能具有相应的活性和相应的生物学功能。</span><span
style='font-size:10.0pt;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:
"Times New Roman"'>了解蛋白质的空间结构不仅有利于认识蛋白质的功能，也有利于认识蛋白质是如何执行其功能的。确定蛋白质的结构对于生物学研究是非常重要的。目前，蛋白质序列数据库的数据积累的速度非常快，但是，已知结构的蛋白质相对比较少。尽管蛋白质结构测定技术有了较为显著的进展，但是，通过实验方法确定蛋白质结构的过程仍然非常复杂，代价较高。因此，实验测定的蛋白质结构比已知的蛋白质序列要少得多。另一方面，随着</span><span
lang=EN-US style='font-size:10.0pt'>DNA</span><span style='font-size:10.0pt;
mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>测序技术的发展，人类基因组及更多的模式生物基因组已经或将要被完全测序，</span><span
lang=EN-US style='font-size:10.0pt'>DNA</span><span style='font-size:10.0pt;
mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>序列数量将会急增，而由于</span><span
lang=EN-US style='font-size:10.0pt'>DNA</span><span style='font-size:10.0pt;
mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>序列分析技术和基因识别方法的进步，我们可以从</span><span
lang=EN-US style='font-size:10.0pt'>DNA</span><span style='font-size:10.0pt;
mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>推导出大量的蛋白质序列。这意味着已知序列的蛋白质数量和已测定结构的蛋白质数量（如蛋白质结构数据库</span><span
lang=EN-US style='font-size:10.0pt'>PDB</span><span style='font-size:10.0pt;
mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>中的数据）的差距将会越来越大。人们希望产生蛋白质结构的速度能够跟上产生蛋白质序列的速度，或者减小两者的差距。那么如何缩小这种差距呢？我们不能完全依赖现有的结构测定技术，需要发展理论分析方法，这对蛋白质结构预测提出了极大的挑战。</span><span
lang=EN-US style='font-size:10.0pt'>20</span><span style='font-size:10.0pt;
mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>世纪</span><span
lang=EN-US style='font-size:10.0pt'>60</span><span style='font-size:10.0pt;
mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>年代后期，</span><span
lang=EN-US style='font-size:10.0pt'>Anfinsen</span><span style='font-size:10.0pt;
mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>首先发现去折叠蛋白或者说<span
style='mso-bidi-font-weight:bold'>变性</span></span><span lang=EN-US
style='font-size:10.0pt;mso-bidi-font-weight:bold'>(denatured)</span><span
style='font-size:10.0pt;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:
"Times New Roman"'>蛋白质在允许重新折叠的实验条件下可以重新折叠到原来的结构，这种<span style='mso-bidi-font-weight:
bold'>天然结构</span></span><span lang=EN-US style='font-size:10.0pt;mso-bidi-font-weight:
bold'>(native structure)</span><span style='font-size:10.0pt;mso-ascii-font-family:
"Times New Roman";mso-hansi-font-family:"Times New Roman"'>对于蛋白质行使生物功能具有重要作用，大多数蛋白质只有在折叠成其天然结构的时候才能具有完全的生物活性。自从</span><span
lang=EN-US style='font-size:10.0pt'>Anfinsen</span><span style='font-size:10.0pt;
mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>提出蛋白质折叠的信息隐含在蛋白质的一级结构中，科学家们对蛋白质结构的预测进行了大量的研究，分子生物学家将有可能直接运用适当的算法，从氨基酸序列出发，预测蛋白质的结构。本章主要着重介绍蛋白质二级结构及空间结构预测的方法。</span><span
lang=EN-US><o:p></o:p></span></p>

<h2 align=center style='text-align:center'><!--mstheme--><span lang=EN-US
style='font-family:隶书;color:#EFCE8F'>7.1 引言 </span><span lang=EN-US><o:p></o:p></span></h2>

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<p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto;
text-indent:21.25pt;line-height:150%'><span style='font-size:10.0pt;font-family:
宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>基因是生命的蓝图，蛋白质是生命的机器。来自于四种字符字母表（</span><span
lang=EN-US style='font-size:10.0pt'>A</span><span style='font-size:10.0pt;
font-family:宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:
"Times New Roman"'>，</span><span lang=EN-US style='font-size:10.0pt'>T</span><span
style='font-size:10.0pt;font-family:宋体;mso-ascii-font-family:"Times New Roman";
mso-hansi-font-family:"Times New Roman"'>（</span><span lang=EN-US
style='font-size:10.0pt'>U</span><span style='font-size:10.0pt;font-family:
宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>），</span><span
lang=EN-US style='font-size:10.0pt'>C</span><span style='font-size:10.0pt;
font-family:宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:
"Times New Roman"'>，</span><span lang=EN-US style='font-size:10.0pt'>G</span><span
style='font-size:10.0pt;font-family:宋体;mso-ascii-font-family:"Times New Roman";
mso-hansi-font-family:"Times New Roman"'>）的核酸序列中蕴藏着生命的信息，而蛋白质则执行着生物体内各种重要的工作，如生物化学反应的催化、营养物质的输运、</span><span
style='font-size:10.0pt;mso-bidi-font-size:8.0pt;font-family:宋体;mso-ascii-font-family:
"Times New Roman";mso-hansi-font-family:"Times New Roman"'>生长</span><span
style='font-size:10.0pt;font-family:宋体;mso-ascii-font-family:"Times New Roman";
mso-hansi-font-family:"Times New Roman"'>和分化控制、生物信号的识别和传递等。蛋白质序列由相应的核酸序列所决定，通过对基因的转录和翻译，将原来四字符的</span><span
lang=EN-US style='font-size:10.0pt'>DNA</span><span style='font-size:10.0pt;
font-family:宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:
"Times New Roman"'>序列，根据三联密码规则翻译成</span><span lang=EN-US style='font-size:10.0pt'>20</span><span
style='font-size:10.0pt;font-family:宋体;mso-ascii-font-family:"Times New Roman";
mso-hansi-font-family:"Times New Roman"'>字符的蛋白质氨基酸序列。</span><span lang=EN-US><o:p></o:p></span></p>

<p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto;
text-indent:21.25pt;line-height:150%'><span style='font-size:10.0pt;font-family:
宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>蛋白质具有不同的长度、不同的氨基酸排列和不同的空间结构，实验分析表明蛋白质能够形成特定的结构。</span><span
style='font-size:10.0pt;mso-bidi-font-size:8.0pt;font-family:宋体;mso-ascii-font-family:
"Times New Roman";mso-hansi-font-family:"Times New Roman"'>蛋白质</span><span
style='font-size:10.0pt;font-family:宋体;mso-ascii-font-family:"Times New Roman";
mso-hansi-font-family:"Times New Roman"'>中相邻的氨基酸通过肽键形成一条伸展的链，肽链上的氨基酸残基形成局部的二级结构，各种二级结构组合形成完整的折叠结构。蛋白质分子很大，其折叠的空间结构会将一些区域包裹在内部，而将其它的区域暴露在外。在蛋白质的空间结构中，序列上相距比较远的氨基酸可能彼此接近。在水溶液中，肽链折叠成为特定的三维结构。主要的驱动力来自于氨基酸残基的疏水性，氨基酸残基的疏水性要求将氨基酸疏水片段放置于分子的内部。<span
style='color:blue'>图</span></span><span lang=EN-US style='font-size:10.0pt;
color:blue'>7.1</span><span style='font-size:10.0pt;font-family:宋体;mso-ascii-font-family:
"Times New Roman";mso-hansi-font-family:"Times New Roman";color:blue'>（</span><span
lang=EN-US style='font-size:10.0pt;color:blue'>a</span><span style='font-size:
10.0pt;font-family:宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:
"Times New Roman";color:blue'>）</span><span style='font-size:10.0pt;font-family:
宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>是酪氨酸磷酸酶的蛋白质序列，<span
style='color:blue'>图</span></span><span lang=EN-US style='font-size:10.0pt;
color:blue'>7.1</span><span style='font-size:10.0pt;font-family:宋体;mso-ascii-font-family:
"Times New Roman";mso-hansi-font-family:"Times New Roman";color:blue'>（</span><span
lang=EN-US style='font-size:10.0pt;color:blue'>b</span><span style='font-size:
10.0pt;font-family:宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:
"Times New Roman";color:blue'>）</span><span style='font-size:10.0pt;font-family:
宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>是对应的二级结构，其中</span><span
lang=EN-US style='font-size:10.0pt'>H </span><span style='font-size:10.0pt;
font-family:宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:
"Times New Roman"'>代表螺旋，</span><span lang=EN-US style='font-size:10.0pt'>E </span><span
style='font-size:10.0pt;font-family:宋体;mso-ascii-font-family:"Times New Roman";
mso-hansi-font-family:"Times New Roman"'>代表折叠，</span><span lang=EN-US
style='font-size:10.0pt'>B</span><span style='font-size:10.0pt;font-family:
宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>表示</span><span
lang=EN-US style='font-size:10.0pt;mso-bidi-font-family:"Courier New"'>β</span><span
style='font-size:10.0pt;font-family:宋体;mso-ascii-font-family:"Times New Roman";
mso-hansi-font-family:"Times New Roman"'>桥，</span><span lang=EN-US
style='font-size:10.0pt'>G</span><span style='font-size:10.0pt;font-family:
宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>表示</span><span
lang=EN-US style='font-size:10.0pt'>310</span><span style='font-size:10.0pt;
font-family:宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:
"Times New Roman"'>螺旋，</span><span lang=EN-US style='font-size:10.0pt'>I</span><span
style='font-size:10.0pt;font-family:宋体;mso-ascii-font-family:"Times New Roman";
mso-hansi-font-family:"Times New Roman"'>表示</span><span lang=EN-US
style='font-size:10.0pt;mso-bidi-font-family:"Courier New"'>π</span><span
style='font-size:10.0pt;font-family:宋体;mso-ascii-font-family:"Times New Roman";
mso-hansi-font-family:"Times New Roman"'>螺旋，</span><span lang=EN-US
style='font-size:10.0pt'>T</span><span style='font-size:10.0pt;font-family:
宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>表示氢键转角，</span><span
lang=EN-US style='font-size:10.0pt'>S</span><span style='font-size:10.0pt;
font-family:宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:
"Times New Roman"'>代表转向，<span style='color:blue'>图</span></span><span
lang=EN-US style='font-size:10.0pt;color:blue'>7.1</span><span
style='font-size:10.0pt;font-family:宋体;mso-ascii-font-family:"Times New Roman";
mso-hansi-font-family:"Times New Roman";color:blue'>（</span><span lang=EN-US
style='font-size:10.0pt;color:blue'>c</span><span style='font-size:10.0pt;
font-family:宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:
"Times New Roman";color:blue'>）</span><span style='font-size:10.0pt;font-family:
宋体;mso-ascii-font-family:"Times New Roman";mso-hansi-font-family:"Times New Roman"'>显示的是该蛋白质的折叠结构。</span><span
lang=EN-US><o:p></o:p></span></p>

<p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto;
text-indent:21.25pt;line-height:150%'><span style='font-size:10.0pt;font-family: