【作者】 姜舟婷；

【导师】 章林溪； 叶高翔；

【作者基本信息】 浙江大学 ， 凝聚态物理， 2005， 博士

【摘要】 生物大分子是通过复杂结构来体现其特殊生物功能的高分子链,是生命活动的主要物质基础。生物大分子包括蛋白质、核酸、多糖、脂类等。这些生物分子只有在特定的三维结构中才能发挥其生物活性。本文的工作主要是针对蛋白质、脱氧核糖核酸以及多糖类凝胶的构象进行理论分析和模拟计算。研究这些生物分子的自然结构以及形成这些结构的机理具有十分重要的意义,它是了解生物体的基础。在本文第二章中,我们基于蛋白质粗粒化和原子历经这两种不同的模型,对蛋白质三维结构中的紧密接触对性质进行统计规律的研究。在蛋白质粗粒化模型中,统计结果告诉我们：疏水性氨基酸(Leu, Val, Ile, Met, Phe, Tyr, Cys和Trp)容易形成长程紧密接触对,亲水性氨基酸(Glu, Gln, Asp, Asn, Lys, Ser, Arg和Pro)则不容易形成长程紧密接触对。氨基酸之间形成的长程紧密接触对起到稳定蛋白质结构的作用,而氨基酸形成短程紧密接触对的能力主要依赖于蛋白质的一维序列。对球状蛋白质来说,全α类型最不容易形成连续的长程紧密接触对,全β类型最容易形成连续的长程紧密接触对,这和它们的二级结构密切相关。考虑到组成氨基酸不同原子间的相互作用力,我们又提出了原子历经模型。该模型证实了氨基酸形成长程紧密对的能力可以严格按照氨基酸的疏水性量度来区分,因此,原子历经模型对蛋白质三维结构的描述更为精细和有效。在蛋白质折叠速率的研究中,同样涉及到蛋白质的三维结构。研究发现：折叠速率Kf和蛋白质的接触序参数CO、TCD和LRO之间都存在着一定的联系。蛋白质折叠速率和TCD之间的线性关系最佳,为lnΚf=-13.2×TCD+19.73。此外,我们提出用BP神经网络模型对蛋白质的折叠速率进行预测。在该模型中,三种接触序参数作为训练BP神经网络的输入节点对蛋白质的折叠速率进行预测比TCD更具有优势。这说明在蛋白质的折叠过程中,不同作用程的接触序参数需同时考虑。这些研究,使我们进一步了解蛋白质的结构性质和形成机理,为蛋白质的结构预测作准备。在本文第三章中,首先我们运用弹性竿模型研究DNA分子的结构和能量之间的关系。通过Monte Carlo方法对DNA分子的构象进行研究发现,DNA分子的弯曲势能量EB比扭转势能量ET大一至两个数量级,均方回转半径与链长成二次函数。其次,考虑到核苷酸之间的近程相关性,我们提出新的DNA二维行走模型,在这个模型下得到许多物理参量如均方末端距<R2(ι)>、均方位移偏差F(ι)的长程相关性和自相关性。同时,通过对能谱分析发现,编码DNA在3.33×10-1 bp-1处有一个明显的峰值,而非编码DNA没有这个峰值,这为区分DNA提供一条新途径。最后,通过对DNA这类刚性高分子链动力学行为的研究,得到弛豫时间和持久长度之间的关系,在柔性链极限下,弛豫时间满足Rouse模型τn∝L2n-2；在刚性链极限下,弛豫时间τn∝[L/(2n-1)]4。这些研究结果涉及DNA的一级结构(序列)、三维结构(空间构象)和动力学行为,系统的研究为进一步了解DNA的结构和生物功能提供了理论依据。在本文第四章中,我们采用实验方法对不同离子源的结冷胶在玻璃基底表面的摩擦行为进行研究。结冷胶是多糖凝胶的一种,在工业上具有广泛的用途。在我们的工作中发现,不管是Na+-结冷胶还是Ca2+-结冷胶都具有非常低的摩擦系数,特别是在运动速度较小的情况下,这使它具有动物关节替代品的独特优势。由不同离子源形成的结冷凝胶的摩擦特性并不相同,原因在于其不同的交联方式。此外还发现结冷胶在水溶液中并不稳定,一定的时间范围内,摩擦系数会随着浸润时间的增加而增加,这是由于形成结冷凝胶的网络结构不稳定造成的。这些研究揭示了凝胶的摩擦机理,同时为开拓结冷胶新的应用领域提供了理论支持。更多还原

【Abstract】 Biopolymers, which have the complicated and compact conformations to embody their biological function, are a physical foundation of the life. Biopolymers include protein, nucleic acid, polysaccharide and lipid. These biopolymers need the specific three-dimensional structure to play their functions. In this dissertation, our main purpose is to uncover the structure property of proteins, DNA and polysaccharide gel. It’s important to study the folded conformations and folding mechanism that is the key point to understand the biology.In Chapter 2, we have investigated statistical properties of contacts based on two models, which called coarse model and each atom counted model. By analyzing the effects of amino acid residue on long- and short-range contacts in coarse model, we can conclude that hydrophobic residues, such as Leu, Val, Ile, Met, Phe, Tyr, Cys, and Trp are easy to form long-range contacts, while hydrophilic residues, such as Glu, Gln, Asp, Asn, Lys, Ser, Arg, and Pro are difficult to form long-range contacts. Long-range contacts contribute more functions to protein folding and play an active role in the stability of proteins. However, the ability to form short-range contacts only depends on the protein sequence. Statistical properties of contacts in globular proteins are also studied. The results show us that different globular proteins have different ability to form contacts, i.e., all-αproteins are difficult to form sequential long-range contacts, while all-βproteins are easy to form it, which strongly depended on their secondary structure. Considering different side group structure and interaction between each atom in a residue, new atom pair contacts are introduced in the each atom counted model. In this model, the ability to form long-range atom pair contacts can be well described by the hydrophobicity scale of the residue in detail. Therefore, it’s more effective to characterize the conformation of proteins, especially in protein folding rate prediction. There is the relationship between the protein folding rateΚfand the contact order (CO), total contact distance (TCD) and long-range order (LRO). Comparing these three parameters, TCD is more effective to predicting folding rate and a relationship is lnKf= -13.2×TCD+19.73. The new prediction method by BP neural network model is also investigated here and more accurate result is obtained. In this model that CO, LRO and TCD are treated as input nodes to predicte protein folding rate is more effective than TCD. It is concluded that the folded structure of a protein depends on CO, LRO and TCD simultaneously. These results can help us to understand the property of protein structure and its mechanism of folding well.In Chapter 3, the relationship between the conformation and energy of DNA is studied under the elastic rod model by Metropolis Monte Carlo simulation firstly. The bending energy EB is about 10 - 102 times larger than twisting energy ET. The relationship between the mean square distance R2g and chain length is also found. Second, the new two-dimensional walk model of DNA, with considering a pair of sequential nucleotides is introduced here. Some linear correlations are obtained in the double logarithmic plots of mean square distance< R2 (l)> and fluctuation F(l) versus nucleotide distance l along DNA chains. In the study of power spectrums, the difference between coding and no-coding DNA sequence is that there is a notable peak value occurs at 3.33×10-1bp-1 in coding DNA sequence. Finally, the Hamilton actuating quantity considering the bending and stretching elastic potential energy is calculated to investigate the dynamic property of polymers. The dependence of the relaxation time on the persistence length is also discussed here. In the flexible limit, the expression of the relaxation timeτn is the same as one in the Rouse mode, i.e.τn∝L2n-2. In the stiff-chain case, such as DNA chains, the expression of the relaxation time isτn∝[L/(2n-1)]4. These analyses include the primary structure (DNA sequence), tertiary structure (DNA conformation) and the dynamic property of DNA, which help us to obtain more detailed information on DNA.In Chapter 4, the frictional behavior of different counterions gellan gel against a glass plate is investigated. Gellan gel is one of the polysaccharide gels, which are widely used in the food industry. The low friction coefficients are observed on either Na+-gellan or Ca2+ -gellan gel measured in pure water or high concentration salt solution, especially the samples rotated under the low angular velocity. It’s the advantage as artificial cartilage materials. The fictional behavior of different counterion gellan gel is not same because of different formation type of double-helical junction-zones, followed by aggregation of the double-helical segments. On the other hand, the frictional stresses of gellan gels are increasing with the increase of immersion time. The observed specific phenomenon seems to be originated from the instability of the network of gellan gel. These results are useful to utilize its full potential as a functional ingredient for foods and biotechnology materials.更多还原