蛋白质结构、运动与功能
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摘要
蛋白质三维 (3D) 结构数量近期的激增使得理解其结构与生物功能之间关系的需求变得愈加迫切了。本文致力于比较蛋白质主链的(-折叠片拓扑，识别侧链的组合，并将结构的运动性引入二级结构和构象，且用智能高分子催化剂来模拟酶活性部位的涨落。
主链的拓扑是一种简化的蛋白质3D结构框架。对(-折叠片的拓扑进行描述具有简捷精炼的特点。我们提出一个用二维矩阵表示蛋白质(-拓扑的普适性比对方法，并对一些蛋白质结构重新进行分类，从而观察到不同的拓扑具有执行其特定功能的倾向。
为了识别可能的侧链相互作用，统计分析的目的是发现氨基酸多元组 (包括二元组、三元组、四元组和五元组) 中频繁出现的组合。我们建立一个方程和图式，为在不同的氨基酸极性和丰度上预测所有的二元组和基于组氨酸的三元组中的侧链组合提供了机会。
二级结构预测的准确率一般不超过75.%。我们计数出序列完全相同的蛋白质链中有15.9～38.1.%.的二级结构处于摆动性的不确定状态，只有平均73.18.%.的二级结构能被氨基酸序列所决定。这种摆动包括(-螺旋/环域和(-折叠股/环域的可逆变换。
构象涨落是结构与功能之间的不可或缺的桥梁。序列全同蛋白质的立体叠合能显示出构象的涨落。对一个蛋白质反复的测定就好像给正在“变形着”的蛋白质实体拍摄了许多照片。X-晶体学也能像核磁共振那样产生蛋白质的“溶液结构”。构象涨落则可能与实现特定功能的结构密切相关。
酶模拟已成为理解催化机制的有效方法。我们合成了既含有催化基团又含电响应基团的高分子催化剂。这些聚合物在无电场时吸纳水分子；在电场存在下则吐出水分子。交变电信号可引发催化剂内部活性洞穴“开”和“闭”往复转换。随着电刺激频率的增加反应速率常数将出现一个极大值。这一现象可被解释为活性部位的涨落促进了底物分子向催化剂核心的扩散，更重要的是，当电刺激的频率与催化剂/底物相互作用的固有频率相等时，催化循环将发生“共振”。这种共振效应可推论到酶催化的机制，蛋白质的构象被认为是处在每秒109次的涨落状态之中
The recent rapid increase in the number of available protein three-dimensional (3D) structures has further highlighted the necessity to understand the relationship between biological function and structure. Given the structure of a protein, how can its evolution source and biological function be determined? This is a problem vitally important to both molecular biologists and bioinformatists today. We herein become interests in comparing (-sheet topologies of protein main-chain, identifying combination of the side-chain, introducing structural mobility into secondary structure and conformation, and simulating enzyme active site fluctuation by intelligent polymer catalysts.
An understanding of the similarities and differences between protein structures is very important for the relationship between structure and function, and for the analysis of possible evolutionary relationships. A main-chain topology is a representation of a protein 3D structural framework. The topological description of (-sheet has the advantage of simplicity, which makes it possible to implement very fast search and comparison algorithms. Here, we present a general approach for aligning a pair of protein (-topologies represented by two-dimensional matrices. The concise view leads to reclassification of protein structures. We observe that the major (-topological classes have different propensities to carry out certain broad categories of functions.
They may be highly specific 3D arrangements of amino acid side-chains in proteins sharing the same catalytic mechanism, but having completely different folds. The classic examples are the proteases, which not only perform the same function despite having totally different structures, but have evolved the same Asp-His-Ser catalytic-triad mechanism. In order to recognize presumptive sidechain interactions, the purpose of the statistical analysis is to find frequently occurring common parts of amino acid polyads, including diads, triads, tetrads and
pentads. At the conclusion of the analysis we are able to construct equation and maps giving the chance that side-chain contacts of the diads and histidine-based triads can be approximately predicted at different degrees of amino acid polarity and abundance.
At present, accuracies for a variety of the secondary structural predictions scarcely go beyond 75.% in general. Which causes, methods of the theoretic prediction have a flaw, or not all the secondary structures are determined by amino acid sequence? There is considerable redundancy in the protein structural databases, as many protein pairs are identical or very similar in sequence. However, we find that 15.9-38.1.% of the secondary structures are in the state of wobble, and only average 73.18.% of the secondary structure can determined by amino acid sequence. The wobble comprises (-helix/loop and (-strand/loop transitions and play an important role in conformational flexibility.
Given the secondary structural wobble, the next question to ask is how the wobble might be translated into a conformational fluctuation. Structure determination is clearly a critical step toward understanding biological function, but protein function requires motion. The conformational fluctuation analysis is the link between structure and function. X-ray diffraction analyses yield accurate static structures of crystalline proteins. The stereo superposition of several sequence-identified proteins can illustrate the conformational fluctuation. Crystallization can "freeze" the fluctuating conformations into a static intermediate sub-state. It is impossible for different laboratories to be equal to each other in crystal packing environments. The repeated determinations for one protein are just like shooting many photographs of an "amoeboid" protein entity. Therefore, X-ray diffraction analyses can also yield "solution structure" of proteins like NMR spectroscopy. Protein fluctuation may be intimately related to the way a structures fulfills a particular function.
Enzyme simulation has become a powe
主链的拓扑是一种简化的蛋白质3D结构框架。对(-折叠片的拓扑进行描述具有简捷精炼的特点。我们提出一个用二维矩阵表示蛋白质(-拓扑的普适性比对方法，并对一些蛋白质结构重新进行分类，从而观察到不同的拓扑具有执行其特定功能的倾向。
为了识别可能的侧链相互作用，统计分析的目的是发现氨基酸多元组 (包括二元组、三元组、四元组和五元组) 中频繁出现的组合。我们建立一个方程和图式，为在不同的氨基酸极性和丰度上预测所有的二元组和基于组氨酸的三元组中的侧链组合提供了机会。
二级结构预测的准确率一般不超过75.%。我们计数出序列完全相同的蛋白质链中有15.9～38.1.%.的二级结构处于摆动性的不确定状态，只有平均73.18.%.的二级结构能被氨基酸序列所决定。这种摆动包括(-螺旋/环域和(-折叠股/环域的可逆变换。
构象涨落是结构与功能之间的不可或缺的桥梁。序列全同蛋白质的立体叠合能显示出构象的涨落。对一个蛋白质反复的测定就好像给正在“变形着”的蛋白质实体拍摄了许多照片。X-晶体学也能像核磁共振那样产生蛋白质的“溶液结构”。构象涨落则可能与实现特定功能的结构密切相关。
酶模拟已成为理解催化机制的有效方法。我们合成了既含有催化基团又含电响应基团的高分子催化剂。这些聚合物在无电场时吸纳水分子；在电场存在下则吐出水分子。交变电信号可引发催化剂内部活性洞穴“开”和“闭”往复转换。随着电刺激频率的增加反应速率常数将出现一个极大值。这一现象可被解释为活性部位的涨落促进了底物分子向催化剂核心的扩散，更重要的是，当电刺激的频率与催化剂/底物相互作用的固有频率相等时，催化循环将发生“共振”。这种共振效应可推论到酶催化的机制，蛋白质的构象被认为是处在每秒109次的涨落状态之中
The recent rapid increase in the number of available protein three-dimensional (3D) structures has further highlighted the necessity to understand the relationship between biological function and structure. Given the structure of a protein, how can its evolution source and biological function be determined? This is a problem vitally important to both molecular biologists and bioinformatists today. We herein become interests in comparing (-sheet topologies of protein main-chain, identifying combination of the side-chain, introducing structural mobility into secondary structure and conformation, and simulating enzyme active site fluctuation by intelligent polymer catalysts.
An understanding of the similarities and differences between protein structures is very important for the relationship between structure and function, and for the analysis of possible evolutionary relationships. A main-chain topology is a representation of a protein 3D structural framework. The topological description of (-sheet has the advantage of simplicity, which makes it possible to implement very fast search and comparison algorithms. Here, we present a general approach for aligning a pair of protein (-topologies represented by two-dimensional matrices. The concise view leads to reclassification of protein structures. We observe that the major (-topological classes have different propensities to carry out certain broad categories of functions.
They may be highly specific 3D arrangements of amino acid side-chains in proteins sharing the same catalytic mechanism, but having completely different folds. The classic examples are the proteases, which not only perform the same function despite having totally different structures, but have evolved the same Asp-His-Ser catalytic-triad mechanism. In order to recognize presumptive sidechain interactions, the purpose of the statistical analysis is to find frequently occurring common parts of amino acid polyads, including diads, triads, tetrads and
pentads. At the conclusion of the analysis we are able to construct equation and maps giving the chance that side-chain contacts of the diads and histidine-based triads can be approximately predicted at different degrees of amino acid polarity and abundance.
At present, accuracies for a variety of the secondary structural predictions scarcely go beyond 75.% in general. Which causes, methods of the theoretic prediction have a flaw, or not all the secondary structures are determined by amino acid sequence? There is considerable redundancy in the protein structural databases, as many protein pairs are identical or very similar in sequence. However, we find that 15.9-38.1.% of the secondary structures are in the state of wobble, and only average 73.18.% of the secondary structure can determined by amino acid sequence. The wobble comprises (-helix/loop and (-strand/loop transitions and play an important role in conformational flexibility.
Given the secondary structural wobble, the next question to ask is how the wobble might be translated into a conformational fluctuation. Structure determination is clearly a critical step toward understanding biological function, but protein function requires motion. The conformational fluctuation analysis is the link between structure and function. X-ray diffraction analyses yield accurate static structures of crystalline proteins. The stereo superposition of several sequence-identified proteins can illustrate the conformational fluctuation. Crystallization can "freeze" the fluctuating conformations into a static intermediate sub-state. It is impossible for different laboratories to be equal to each other in crystal packing environments. The repeated determinations for one protein are just like shooting many photographs of an "amoeboid" protein entity. Therefore, X-ray diffraction analyses can also yield "solution structure" of proteins like NMR spectroscopy. Protein fluctuation may be intimately related to the way a structures fulfills a particular function.
Enzyme simulation has become a powe
引文