点突变是基因内部发生了改变，指组成基因的脱氧核苷酸的种类、数量、排列顺序发生了改变，由于基因发生了改变，所以性状也就产生了变异。这是一个重要的生物过程，与许多遗传疾病相关。目前的研究工作聚焦在丙氨酸到苯丙氨酸在脯氨酸环境下的突变上。采用密度泛函方法，在6-31G(d)的理论水平上，对Pro-Ala-Pro和Pro-Phe-Pro进行结构优化。本文采用量子化学方法从主链折叠、支链取向、-转角结构和酰胺值四个方面对Pro-Ala-Pro和Pro-Phe-Pro的稳定构象进行了理论研究。在Pro-X-Pro三肽的LxL构象中两个脯氨酸残基的值和ψ值分别约为-80º和73º。其中‘X’是一个自然存在的氨基酸残基。包含-转角结构的比扩展二次结构的缩氨酸键受到攻击更易分裂。丙氨酸到苯丙氨酸的突变也有一个显著的能量偏差。Pro-Phe-Pro构象的相对能量值约比Pro-Ala-Pro构象高23%。扩展构象LLL在第一个肽键中酰胺值增长了15%，第二个肽键中酰胺值则增长了21%。因此，肽键的稳定态是一个相当大的“能量储蓄罐”，比由于丙氨酸到苯丙氨酸的点突变而丢失的能量大的多。具有（弱）极性作用中的氢键对于生物活性非常重要，并且对很多种分子的几何和电子结构有很大的影响，因此，此论文利用Bader的分子中的原子理论对Pro-Ala-Pro和Pro-Phe-Pro的分子内氢键进行了相关电子密度拓扑分析。本论文设计了六个氢键类型（从A到F）来研究这两个三肽中的氢键网络结构；量化了氢键长度与键（环）鞍点电子密度和拉普拉斯电子密度，以及 的关系；也研究了键长与其对应的键角和二面角的关系。沿着环鞍点电子密度的减少，环元素从五元环增到十元环。七元环是最稳定的含氢键环。揭示了形成氢键的环类型和大小在形成相应的氢键过程中扮演着非常重要的角色。分子中的原子理论分析也确定了分子必须非常紧凑才能尽可能的形成氢键的逻辑关系。这就是说分子的氢键作用力越强，则分子内部的抵抗力越强。从平衡角度，最后的结果是零点能真正的增长。这些结果旨在帮助缩氨酸和蛋白质折叠建立氢键网络规则。点突变的影响可以被分为两部分：氨基酸变化和结构变化；这两种变化都会改变分子内作用。为了帮助理解氨基酸变化的结果，此文通过研究Pro-Ala-Pro → Pro-Phe-Pro突变过程中的几何构象和热函变化参数来量化分析变化过程。由结构变化和点突变组成的Born-Haber热循环提供丙氨酸到苯丙氨酸（Ala → Phe）点突变的能量结果信息。点突变的自由能变化被分成三个不同的区域，一个区域是在-5和-15 kcal/mol之间，构象从 变化到 ，中心氨基酸变化从D-到L-异构体，所有的变化是放热的。另一个区域∆G为正值从5到15 kcal/mol，构象变化从 到 ，中心氨基酸构象变化从L-到D-异构体，所有的变化是吸热的。第三个区域ΔG值均布居在零值附近，它们的构象是在 或者 之间互相转换，中心氨基酸没有异构体的转换。在免疫球蛋白中， Pro-Xxx-Pro这样的三肽组合是非常重要的弯曲铰链模块组成部分。本论文分析了其构造生物友好纳米结构链的可能性，并为今后研究点突变在遗传疾病和物种消失中的重要作用奠定了基础。

A point mutation is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic material. Often the term point mutation also includes insertions or deletions of a single base pair. Point mutation is an important bio-chemical process related to many genetically transmitted diseases. The present work focuses on Ala → Phe mutation through analysis of the geometric and energetic consequences of such structural changes. Employing Density Functional Theory, Pro-Ala-Pro and Pro-Phe-Pro tri-peptide models were geometry optimised at the B3LYP/6-31G(d) level of theory. Quantum chemical method was used to study the four aspects, backbold folding, side chain orientation, -turn structure, and amidicity analysis, for the two tripeptides. The value of both prolyl residues in the conformations can be maintained at  = ~-80º and ψ = ~73º, in Pro-X-Pro tripeptides, where ‘X’ is a naturally occurring amino acid residues. -turns are more vulnerable to the cleavage of the peptide bond involved in the -turn than those of extended secondary structures. The Ala → Phe mutation makes a noticeable energetic difference, where the relative energies of Pro-Phe-Pro conformers are ~23% higher than those of the Pro-Ala-Pro conformers. The amidicity of the extended conformation also has a 15% and 21% increase in the cases of the 1st and 2nd peptide bonds, respectively. Thus, stabilisation of the peptide bonds is a considerably larger energy ‘reservoir’ than the lost stability due to the Ala → Phe point mutation. Hydrogen bonds among weakly polar interactions are essential to bioactivity and can also be highly influential to the geometry and electronic structures. Therefore, intra-molecular hydrogen bonding in Pro-Ala-Pro and Pro-Phe-Pro has been characterised using Bader’s Atoms in Molecules (AIM) analysis of relevant electron density topologies. Six types (A-F) were proposed to study the network of hydrogen bonds in the two diamides. The relationship between hydrogen bond lengths, electron densities, Laplacian of electron densities, as well as the elongation ( ) of electron densities at bond and ring critical points were so quantified. The correlation of hydrogen bonds length (X-H) with corresponding bond angles (X-H•••M) and dihedral angles (X-H•••M-Y) were also investigated. Along the decrease of electron densities at RCPs, were examined for ring sizes from five- to ten-membered hydrogen-bound rings; seven-membered rings the most favoured. It was suggested that the type and size of rings play a role in the formation of corresponding H-bonds. AIM analysis confirms the logical situation that the molecule has to become very compact to form as many hydrogen bonds as possible. This relatively large hydrogen bond stabilization exerted by the network was compensated by a relatively large internal repulsion due to the compactness of the structures. The net result, on balance, was a very mode increase in the zero point corrected conformation energy ( ). These findings aid in establishing hydrogen-bond rules in reductionist approaches to the peptide and protein folding.The effect of the point mutation can be divided into two parts: the amino acid change and the conformational change; both changing the list of intramolecular interactions. Born-Haber thermodynamic cycles consisting of conformational change as well as point mutation provided information on the energetic consequences of an Ala → Phe point mutation in the two tripeptides. Three distinguishable domains for Ala → Phe mutations are dominated by the ∆G of point mutation. One domain is exothermic in terms of the variation of ∆G from -5 to -15 kcal/mol, in which all the central amino acid of conformers change from D- to L-isomers. Another domain is endothermic, with ∆G ranging from 5 to 15 kcal/mol, conformers changing from to ; i.e. the central amino acid changes from L- to D-isomers. Further conformer changes during Ala → Phe mutation populate the ∆G ≈ 0 ‘neighborhood’, with corresponding conformers changing from to , or from to ; with no isomer change in the central amino acid.Such peptide triads Pro-Xxx-Pro appear to be important flexible hinge modules in immunoglobulines. The possibility to explore if such subunits may be used to build bio-friendly nanostructural arms has been analysed. The important role is studied on the future of point mutation for the hereditary diseases and the annihilation of ones existing in the natural sequence.