人工甜味受体模型识别甜味过程的分子动力学模拟
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摘要
在食品科学领域中,甜味作为5种基本味感之—,它的感官特征的评价一直依赖于人的感官品评。然而,由于品评人员生理和心理方面的差异,对甜真实、客观感受的表达往往受到很大程度的制约。而且,受制于没有得到甜味受体蛋白的确切结构,人们仍然没有完全理解甜味分子的感受机理。因此,构建一种人工甜味受体模型显得尤为重要。
本课题组前期以富勒醇C60(OH)18作为人工甜味受体模型,运用等温滴定量热(ITC)、感官品评、核磁共振(NMR)等实验手段对人工甜味受体模型与人工甜味剂、天然甜味剂、甜味抑制剂、甜味异构体、甜味增强剂的识别作用进行了研究。研究结果表明,富勒醇作为人工受体模型对甜味剂有较好的识别作用,对解释甜味抑制剂和增强剂的机理起到积极作用,并且表现出了各种糖类异构体的甜度差异。本文进一步运用分子动力学(MD)方法：从原子水平上研究了人工甜味受体模型富勒醇与甜味剂、甜味异构体的相互作用,并且.进一步优化人工甜味受体模型结构,以期为甜味机理的研究提供更多的信息。
本课题研究的内容有：
(1)建立了人工甜味受体与甜味剂相互作用的MD模拟方法
在前期建立的人工甜味受体模型实验基础上,选择了六种不同甜味剂进行研究。通过比较果糖、葡萄糖、半乳糖、蔗糖、海藻糖以及麦芽糖与富勒醇相互作用的结合能,可以发现它们之间的结合能变化趋势与甜味剂的甜度具有相关性。对于近乎相同质量分数下的六种甜味剂,它们与富勒醇的结合能大小为：果糖>葡萄糖>半乳糖>庶糖>海藻糖>麦芽糖。在前期等温度定量实验中也发现同样的规律,这说明富勒醇识别不同甜味剂的有效性,以及分子动力学方法的可行性。
(2)人工甜味受体模型富勒醇与甜味剂异构体相互作用的研究
在前期运用ITC和NMR等技术手段研究富勒醇与单糖异构体相互作用的结果表明,富勒醇加入异构体中,富勒醇更易与β型异构体稳定地结合,并且.结合所释放的能量提供了α型异构体向β异型构体构象转化的能量。通过分子动力学模拟结果同样表明,富勒醇更易于β型异构体发生结合,两者的结合能普遍大于与α型异构体的结合能；并且,L型异构体与富勒醇的结合能也普遍大于D型异构体与富勒醇的结合能。
通过比较三种甜味剂与富勒醇的结合方式可以看出,氢键在它们的结合中起到较大的作用,并且它们的结合位点不同,果糖的环状结构部分更易与富勒醇相结合,而半乳糖和葡萄糖的链端部分更易与富勒醇相结合。这一结果为研究甜味剂机理提供了一定的信息。
(3)优化人工甜味受体模型富勒醇分子
一方面由于富勒醇上羟基数量的增加可以使其与甜味分子的可结合位点增多,增加识别作用；另一方面,富勒醇分子羟基数量的过分增加同样也会减小富勒醇表面的疏水作用,富勒醇分子表而的羟基距离太近会导致羟基间相互吸引,从而形成分子内氢键。一旦富勒醇分子形成分子内氢键,则相应的氢原子就不能与其它分子形成分子间氢键,从而不利于人工甜味受体识别甜味剂。因此本论文进一步优化了人工甜味受体模型富勒醇,其结果表明C60(OH)20更适合作为人工甜味受体模型。分子动力学模拟结果表明富勒醇分子内氢键随羟基数德增加而明显增加,进一步证明富勒醇羟基数超过20个时则不利于识别甜味剂。总之,本文在前期实验研究的基础上,采用分子动力学方法,进
一步研究了人工甜味受体模型化合物与甜味剂及其异构体间的相互作用,并进一步优化了模型化合物,建立运用分子动力学方法研究人工甜味受体模型的方法,丰富了甜味机理研究的仿生化学,并将分子动力学方法引入食品科学领域。
Sweetness is a basic taste in the field of food science while there are five basic tastes. Sweetness organoleptic property always lies on panelist sensory evaluation. However, it is difficult to express taste with true feelings and impersonality because of much difference in psychology and physiology of panelists. In addition, researchers still have no integrated comprehension for sweetness mechanism because it has no definite structure of the taste receptor protein. So it is veiy important to construct an artificial sweet taste receptor model.
Recently, our team used C60(OH)18as an artificial sweet taste receptor model, and isothermal titration calorimetry (ITC), sensory evaluation, nuclear magnetic resonance (NMR) as tool to research the recognition of artificial sweet taste receptor model with artificial sweeteners, natural sweeteners, sweetness isomer, sweetness inhibitor and sweetness enhancer. The result showed that fullerenols can effectively recognize sweetness as an artificial sweet taste receptor model, and it is important for researchers to understand sweetness strengthening mechanism and sweetness inhibiting mechanism. This thesis further applies molecular dynamics (MD) simulation approach to research on interaction between artificial sweet taste receptor model with sweetness and sweet isomers, and optimizes the structure of artificial sweet taste receptor model in order to obtain more information about mechanism of sweetness. The main research work is as follows:
(1) The formation for research on interaction between artificial sweet taste receptor with sweetness by MD simulation
The interaction of6sweeteners (Fructose, Glucose, Galactose, Sucrose, Trehalose and Maltose) with fullerenols was researched by molecular dynamics. The result implied that the binding energies of6sweeteners with fullerenols were relational with the sweetness of6sweeteners. In the same condition, beginning with the largest binding energy is:Fructose> Glucose> Galactose> Sucrose> Trehalose> Maltose. Recently, we found the same law in the previous titration experiments of ITC. These show that effectiveness of fullerenols recognize sweeteners, as well as the feasiability of molecular dynamics method.
(2) Research on the interaction of artifical model fullerenols with sweetness isomers
Recently, our team research on the interaction of artifical model fullerenols with sweetness isomers by ITC and NMR technology, and the result shows'that β-isomers and fullerenols has more stable coalition compare with a-isomers. Energy would be released when P-isomers bind with fullerenols, and the energy is necessary for a-isomers transfer into β-isomers. The molecular dynamics simulation experimental result also shows that β-isomers and fullerenols has more stable coalition compare with a-isomers, and the binding energies of β-isomers with fullerenols are greater than a-isomers. However, the binding energies of L-isomers with fullerenols are also greater than D-isomers.
By comparing the way of fullerenols combined with3kinds of sweeteners, it is found that the hydrogen bond play an important role when fullerenols combined with sweeteners. They have different binding site, ring part of the fructose has more stable coalition with fullerenols, and chain end of glucose and galactose have more stable coalition with fullerenols. These results would provide some information about mechanism of sweetness.
(3) Structural optimization of artificial sweetness receptor model fullerenols
On one hand, with the increasing of the number of fullerenols hydroxyl groups, the binding site of fullerenols with sweetness would increase. So, they can make better identification with sweetness. On the other hand, excessive fullerenols hydroxyl groups will decrease hydrophobic interaction, and hydroxyl groups of fullerenols will attract each other to form intramolecular hydrogen bond. In case fullerenols molecular form intramolecular hydrogen bond, the corresponding hydrogen atoms can not form hydrogen bond with other molecular, and it is going against to recognization reaction of fullerenols with sweetness. So, Structural optimization of artificial sweetness receptor model fullerenols is necessary, and the result shows that C60(OH)20is more suitable to be used as artificial sweetness receptor model. The molecular dynamics simulation the result shows intramolecular hydrogen bond would increase when increase the number of fullerenols hydroxyl group, and it is further prove that fullerenols will not suitable to be used as artificial sweetness receptor model to recognize sweetness if the number of hydroxyl group more than20.
In conclusion, this thesis applies molecular dynamics simulation method approach to further study the interaction between artificial sweet taste receptor model with sweetness and sweet isomers, and optimizes the structure of artificial sweet taste receptor model in order to obtain more information about mechanism of sweetness. The purpose of this thesis is to form method for research on artificial sweet taste receptor by molecular dynamics simulation, enrich biomimctic chemistry of sweetness mechanism study, and introduce molecular dynamics method to food science.
本课题组前期以富勒醇C60(OH)18作为人工甜味受体模型,运用等温滴定量热(ITC)、感官品评、核磁共振(NMR)等实验手段对人工甜味受体模型与人工甜味剂、天然甜味剂、甜味抑制剂、甜味异构体、甜味增强剂的识别作用进行了研究。研究结果表明,富勒醇作为人工受体模型对甜味剂有较好的识别作用,对解释甜味抑制剂和增强剂的机理起到积极作用,并且表现出了各种糖类异构体的甜度差异。本文进一步运用分子动力学(MD)方法：从原子水平上研究了人工甜味受体模型富勒醇与甜味剂、甜味异构体的相互作用,并且.进一步优化人工甜味受体模型结构,以期为甜味机理的研究提供更多的信息。
本课题研究的内容有：
(1)建立了人工甜味受体与甜味剂相互作用的MD模拟方法
在前期建立的人工甜味受体模型实验基础上,选择了六种不同甜味剂进行研究。通过比较果糖、葡萄糖、半乳糖、蔗糖、海藻糖以及麦芽糖与富勒醇相互作用的结合能,可以发现它们之间的结合能变化趋势与甜味剂的甜度具有相关性。对于近乎相同质量分数下的六种甜味剂,它们与富勒醇的结合能大小为：果糖>葡萄糖>半乳糖>庶糖>海藻糖>麦芽糖。在前期等温度定量实验中也发现同样的规律,这说明富勒醇识别不同甜味剂的有效性,以及分子动力学方法的可行性。
(2)人工甜味受体模型富勒醇与甜味剂异构体相互作用的研究
在前期运用ITC和NMR等技术手段研究富勒醇与单糖异构体相互作用的结果表明,富勒醇加入异构体中,富勒醇更易与β型异构体稳定地结合,并且.结合所释放的能量提供了α型异构体向β异型构体构象转化的能量。通过分子动力学模拟结果同样表明,富勒醇更易于β型异构体发生结合,两者的结合能普遍大于与α型异构体的结合能；并且,L型异构体与富勒醇的结合能也普遍大于D型异构体与富勒醇的结合能。
通过比较三种甜味剂与富勒醇的结合方式可以看出,氢键在它们的结合中起到较大的作用,并且它们的结合位点不同,果糖的环状结构部分更易与富勒醇相结合,而半乳糖和葡萄糖的链端部分更易与富勒醇相结合。这一结果为研究甜味剂机理提供了一定的信息。
(3)优化人工甜味受体模型富勒醇分子
一方面由于富勒醇上羟基数量的增加可以使其与甜味分子的可结合位点增多,增加识别作用；另一方面,富勒醇分子羟基数量的过分增加同样也会减小富勒醇表面的疏水作用,富勒醇分子表而的羟基距离太近会导致羟基间相互吸引,从而形成分子内氢键。一旦富勒醇分子形成分子内氢键,则相应的氢原子就不能与其它分子形成分子间氢键,从而不利于人工甜味受体识别甜味剂。因此本论文进一步优化了人工甜味受体模型富勒醇,其结果表明C60(OH)20更适合作为人工甜味受体模型。分子动力学模拟结果表明富勒醇分子内氢键随羟基数德增加而明显增加,进一步证明富勒醇羟基数超过20个时则不利于识别甜味剂。总之,本文在前期实验研究的基础上,采用分子动力学方法,进
一步研究了人工甜味受体模型化合物与甜味剂及其异构体间的相互作用,并进一步优化了模型化合物,建立运用分子动力学方法研究人工甜味受体模型的方法,丰富了甜味机理研究的仿生化学,并将分子动力学方法引入食品科学领域。
Sweetness is a basic taste in the field of food science while there are five basic tastes. Sweetness organoleptic property always lies on panelist sensory evaluation. However, it is difficult to express taste with true feelings and impersonality because of much difference in psychology and physiology of panelists. In addition, researchers still have no integrated comprehension for sweetness mechanism because it has no definite structure of the taste receptor protein. So it is veiy important to construct an artificial sweet taste receptor model.
Recently, our team used C60(OH)18as an artificial sweet taste receptor model, and isothermal titration calorimetry (ITC), sensory evaluation, nuclear magnetic resonance (NMR) as tool to research the recognition of artificial sweet taste receptor model with artificial sweeteners, natural sweeteners, sweetness isomer, sweetness inhibitor and sweetness enhancer. The result showed that fullerenols can effectively recognize sweetness as an artificial sweet taste receptor model, and it is important for researchers to understand sweetness strengthening mechanism and sweetness inhibiting mechanism. This thesis further applies molecular dynamics (MD) simulation approach to research on interaction between artificial sweet taste receptor model with sweetness and sweet isomers, and optimizes the structure of artificial sweet taste receptor model in order to obtain more information about mechanism of sweetness. The main research work is as follows:
(1) The formation for research on interaction between artificial sweet taste receptor with sweetness by MD simulation
The interaction of6sweeteners (Fructose, Glucose, Galactose, Sucrose, Trehalose and Maltose) with fullerenols was researched by molecular dynamics. The result implied that the binding energies of6sweeteners with fullerenols were relational with the sweetness of6sweeteners. In the same condition, beginning with the largest binding energy is:Fructose> Glucose> Galactose> Sucrose> Trehalose> Maltose. Recently, we found the same law in the previous titration experiments of ITC. These show that effectiveness of fullerenols recognize sweeteners, as well as the feasiability of molecular dynamics method.
(2) Research on the interaction of artifical model fullerenols with sweetness isomers
Recently, our team research on the interaction of artifical model fullerenols with sweetness isomers by ITC and NMR technology, and the result shows'that β-isomers and fullerenols has more stable coalition compare with a-isomers. Energy would be released when P-isomers bind with fullerenols, and the energy is necessary for a-isomers transfer into β-isomers. The molecular dynamics simulation experimental result also shows that β-isomers and fullerenols has more stable coalition compare with a-isomers, and the binding energies of β-isomers with fullerenols are greater than a-isomers. However, the binding energies of L-isomers with fullerenols are also greater than D-isomers.
By comparing the way of fullerenols combined with3kinds of sweeteners, it is found that the hydrogen bond play an important role when fullerenols combined with sweeteners. They have different binding site, ring part of the fructose has more stable coalition with fullerenols, and chain end of glucose and galactose have more stable coalition with fullerenols. These results would provide some information about mechanism of sweetness.
(3) Structural optimization of artificial sweetness receptor model fullerenols
On one hand, with the increasing of the number of fullerenols hydroxyl groups, the binding site of fullerenols with sweetness would increase. So, they can make better identification with sweetness. On the other hand, excessive fullerenols hydroxyl groups will decrease hydrophobic interaction, and hydroxyl groups of fullerenols will attract each other to form intramolecular hydrogen bond. In case fullerenols molecular form intramolecular hydrogen bond, the corresponding hydrogen atoms can not form hydrogen bond with other molecular, and it is going against to recognization reaction of fullerenols with sweetness. So, Structural optimization of artificial sweetness receptor model fullerenols is necessary, and the result shows that C60(OH)20is more suitable to be used as artificial sweetness receptor model. The molecular dynamics simulation the result shows intramolecular hydrogen bond would increase when increase the number of fullerenols hydroxyl group, and it is further prove that fullerenols will not suitable to be used as artificial sweetness receptor model to recognize sweetness if the number of hydroxyl group more than20.
In conclusion, this thesis applies molecular dynamics simulation method approach to further study the interaction between artificial sweet taste receptor model with sweetness and sweet isomers, and optimizes the structure of artificial sweet taste receptor model in order to obtain more information about mechanism of sweetness. The purpose of this thesis is to form method for research on artificial sweet taste receptor by molecular dynamics simulation, enrich biomimctic chemistry of sweetness mechanism study, and introduce molecular dynamics method to food science.
引文
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