📚 Appendix 1: Amino Acid R Groups | 附录1：氨基酸 R 基团
Amino acids are the monomer units from which all proteins are built. In the Cambridge International A-Level Biology specification, the R group, or side chain, is the part of an amino acid that varies between the 20 common amino acids and is responsible for the different chemical properties that allow proteins to fold into precise three-dimensional shapes.
氨基酸是构成所有蛋白质的单体单位。在剑桥国际 A-Level 生物课程中，R 基团（或称侧链）是 20 种常见氨基酸之间彼此不同的部分，正是这些不同的化学性质使蛋白质能够折叠成精确的三维形状。
This appendix is a reference sheet for revision. It covers what the R group is, how the 20 standard side chains are classified, which bonds they form, and how those bonds build secondary, tertiary and quaternary structure. Every claim below is examinable content for Papers 1, 2 and 4.
本附录是一份复习用参考清单，涵盖 R 基团的定义、20 种标准侧链的分类、它们能形成哪些键，以及这些键如何构建二级、三级和四级结构。以下每一条内容都属于 Paper 1、Paper 2 和 Paper 4 的可考查范围。
1. The Amino Acid Backbone | 氨基酸的基本主链
Every amino acid, from the simplest glycine to the most complex tryptophan, is built on the same scaffold. A central carbon atom, called the α-carbon, is bonded to four different groups: an amino group (–NH₂), a carboxyl group (–COOH), a single hydrogen atom (–H), and the R group. Only the R group changes from one amino acid to the next.
从最简单的甘氨酸到最复杂的色氨酸，每一种氨基酸都建立在同一个骨架之上。一个中心碳原子（称为 α-碳）连接着四个基团：氨基（–NH₂）、羧基（–COOH）、一个氢原子（–H）以及 R 基团。这四者之中，只有 R 基团在不同氨基酸之间发生变化。
H₂N–CH(R)–COOH
In solution at around pH 7, the amino group and the carboxyl group are ionised, so the molecule exists as a zwitterion with no overall charge. This is why amino acids can act as buffers and why they dissolve readily in water.
在 pH 约 7 的溶液中，氨基与羧基都会解离，因此分子以两性离子形式存在，整体不带净电荷。这正是氨基酸能充当缓冲剂、并且易溶于水的原因。
H₃N⁺–CH(R)–COO⁻
When two amino acids join, the carboxyl group of one reacts with the amino group of the next in a condensation reaction, releasing one molecule of water and forming a peptide bond (–CO–NH–). The R groups play no part in this reaction - they are simply carried along on the outside of the polypeptide backbone.
当两个氨基酸连接时，一个的羧基与另一个的氨基发生缩合反应，脱去一分子水并形成肽键（–CO–NH–）。R 基团不参与这一反应——它们只是被"挂在"多肽主链的外侧。
2. Why R Groups Matter | 为什么 R 基团重要
The 20 standard amino acids all share the same basic backbone, but each has a unique R group. The R group determines the amino acid's size, shape, charge, polarity and chemical reactivity. Two amino acids with identical backbones can therefore behave completely differently inside a cell.
20 种标准氨基酸具有相同的基本主链，但每一种都有独特的 R 基团。R 基团决定了氨基酸的大小、形状、电荷、极性和化学反应活性。因此，主链完全相同的两种氨基酸，在细胞内的行为可能截然不同。
During protein folding, side chains interact with one another and with water. These interactions determine whether a chain forms an α-helix, a β-pleated sheet, a hydrophobic core, an active site or a binding surface.
在蛋白质折叠过程中，侧链彼此之间以及与水的相互作用，决定了肽链最终形成 α-螺旋、β-折叠、疏水核心、活性位点还是结合表面。
In other words, the primary structure (the sequence of R groups) dictates the secondary, tertiary and quaternary structure. Change one R group and the whole folded shape can change - which is exactly what happens in sickle-cell anaemia, where a single glutamate is replaced by valine in the β-globin chain.
换言之，一级结构（即 R 基团的排列顺序）决定了二级、三级和四级结构。改变一个 R 基团，整个折叠形状就可能改变——镰状细胞贫血症就是如此：β-珠蛋白链上的一个谷氨酸被缬氨酸取代。
3. A Working Classification of R Groups | R 基团的实用分类
For examination purposes, the 20 R groups are grouped by their chemistry at pH 7 rather than by memorising every structure. Four functional categories are enough: non-polar (hydrophobic), polar uncharged, positively charged, and negatively charged. Aromatic side chains form a useful sub-group because they are large and largely hydrophobic.
从应试角度，不必死记每一种结构，而应按 pH 7 时的化学性质把 20 种 R 基团分类。掌握四个功能类别就足够了：非极性（疏水）、极性不带电、带正电和带负电。芳香族侧链因体积大且大多疏水，可单列为一个子类。
| Amino acid 氨基酸 | R group feature R 基团特征 | Class 类别 | Key behaviour 关键行为 |
|---|---|---|---|
| Glycine | –H | Non-polar | Smallest; maximum flexibility |
| Alanine | –CH₃ | Non-polar | Hydrophobic |
| Valine, Leucine, Isoleucine | Branched alkyl | Non-polar | Fill the hydrophobic core |
| Methionine | –CH₂–CH₂–S–CH₃ | Non-polar | Start codon; sulfur-containing |
| Phenylalanine | –CH₂–C₆H₅ | Aromatic, non-polar | Van der Waals stacking |
| Tryptophan | Indole ring | Aromatic, non-polar | Largest R group |
| Tyrosine | –CH₂–C₆H₄–OH | Aromatic, polar | Can be phosphorylated |
| Serine, Threonine | –OH | Polar uncharged | Hydrogen bonding; phosphorylation |
| Cysteine | –SH | Polar uncharged | Disulfide bridge formation |
| Asparagine, Glutamine | –CONH₂ | Polar uncharged | Hydrogen bonding |
| Lysine | –(CH₂)₄–NH₂ | Basic (+) | Ionic bonds; binds DNA |
| Arginine | Guanidino group | Basic (+) | Strongest positive charge |
| Histidine | Imidazole ring | Basic (+/0) | Buffers and catalyses near pH 7 |
| Aspartate, Glutamate | –COO⁻ | Acidic (–) | Salt bridges; metal binding |
4. Non-Polar Aliphatic R Groups | 非极性脂肪族 R 基团
Glycine, alanine, valine, leucine, isoleucine, methionine and proline have side chains made mainly of carbon and hydrogen. C–H bonds are essentially non-polar, so these side chains cannot form hydrogen bonds with water and are described as hydrophobic.
甘氨酸、丙氨酸、缬氨酸、亮氨酸、异亮氨酸、甲硫氨酸和脯氨酸的侧链主要由碳和氢构成。C–H 键基本上是非极性的，因此这些侧链无法与水形成氢键，被称为疏水性侧链。
In a folded globular protein, these residues are buried in the interior, away from the aqueous cytoplasm. This clustering is called the hydrophobic core, and it is the main driving force that makes a polypeptide collapse into a compact shape.
在折叠的球状蛋白中，这些残基被埋在分子内部，远离含水的细胞质。这种聚集称为疏水核心，是使多肽塌缩成紧凑形状的主要驱动力。
Because they are non-polar, these R groups interact with each other only through weak hydrophobic interactions and van der Waals forces. Individually these forces are tiny, but in a large protein there are so many of them that the total effect is considerable.
由于非极性，这些 R 基团之间只能通过较弱的疏水相互作用和范德华力相互结合。单独看，这些力非常微弱，但在一个大蛋白质中数量极多，总效应相当可观。
5. Aromatic R Groups | 芳香族 R 基团
Phenylalanine, tyrosine and tryptophan contain flat, ring-shaped side chains. The rings are rich in delocalised π electrons, which makes them bulky, relatively rigid and mostly hydrophobic.
苯丙氨酸、酪氨酸和色氨酸含有平面环状侧链。这些环富含离域 π 电子，因此体积大、相对刚性，且大多具有疏水性。
Phenylalanine is purely non-polar and is often found buried inside proteins, where its flat ring stacks against other aromatic rings through van der Waals interactions. Tryptophan is the largest of all the R groups and is frequently found at membrane–water interfaces.
苯丙氨酸完全非极性，常被埋在蛋白质内部，其平面环通过范德华力与其他芳香环堆叠。色氨酸是所有 R 基团中最大的一个，常出现在膜与水的界面上。
Tyrosine is the exception: its –OH group makes it weakly polar, so it can form hydrogen bonds and act as a hydrogen-bond donor. It can also be phosphorylated, making it important in cell signalling pathways.
酪氨酸是个例外：它的 –OH 基团使其带有弱极性，因此能形成氢键并充当氢键供体。它还可以被磷酸化，因而在细胞信号传导通路中十分重要。
6. Polar Uncharged R Groups | 极性不带电 R 基团
Serine, threonine, cysteine, asparagine, glutamine and tyrosine carry –OH, –SH or –CONH₂ groups. Oxygen, nitrogen and sulfur are more electronegative than carbon, so the electrons in these bonds are pulled unequally and the side chain becomes polar.
丝氨酸、苏氨酸、半胱氨酸、天冬酰胺、谷氨酰胺和酪氨酸带有 –OH、–SH 或 –CONH₂ 基团。氧、氮和硫的电负性高于碳，因此这些键中电子分布不均，侧链便具有极性。
Because they are polar but not ionised at pH 7, these side chains form hydrogen bonds with water and with each other, yet they carry no net charge. They are therefore usually found on the surface of globular proteins or lining channels and active sites.
由于在 pH 7 时具有极性但不解离，这些侧链既能与水以及与彼此形成氢键，又不带净电荷。因此它们通常位于球状蛋白表面，或排列在通道与活性位点的内壁。
Serine and threonine are important in enzyme catalysis, where their –OH group can act as a nucleophile or hold a substrate in place. Serine, threonine and tyrosine are also the three residues most commonly modified by phosphorylation in cell signalling.
丝氨酸和苏氨酸在酶催化中很重要，其 –OH 基团可作为亲核试剂或固定底物。此外，丝氨酸、苏氨酸和酪氨酸也是细胞信号传导中最常发生磷酸化修饰的三种残基。
7. Positively Charged (Basic) R Groups | 带正电（碱性）R 基团
Lysine, arginine and histidine contain nitrogen atoms in their side chains that accept protons at physiological pH. Lysine ends in an amino group, arginine carries a guanidino group, and histidine contains an imidazole ring.
赖氨酸、精氨酸和组氨酸的侧链中含有能在生理 pH 下接受质子的氮原子。赖氨酸末端为氨基，精氨酸带有胍基，组氨酸则含有一个咪唑环。
The result is a positive charge: lysine and arginine are fully protonated as –NH₃⁺ and –C(NH₂)₂⁺ at pH 7, while histidine is only partly protonated (roughly 10 % at pH 7.4) because its side-chain pKa is close to 6.
结果就是带正电：在 pH 7 时，赖氨酸和精氨酸完全质子化为 –NH₃⁺ 和 –C(NH₂)₂⁺，而组氨酸只有部分质子化（在 pH 7.4 时约 10 %），因为其侧链 pKa 接近 6。
These positive charges let basic residues form ionic bonds, also called salt bridges, with negatively charged groups. This is why lysine and arginine are abundant in histone proteins, which must bind the negatively charged phosphate backbone of DNA.
这些正电荷使碱性残基能与带负电的基团形成离子键，也称为盐桥。这正是组蛋白中赖氨酸和精氨酸含量丰富的原因——组蛋白必须结合 DNA 带负电的磷酸骨架。
Histidine deserves special attention: because it readily gains and loses a proton near pH 7, it is often found in enzyme active sites where it can donate or accept protons during catalysis, and it also helps proteins buffer small pH changes.
组氨酸值得特别注意：由于它在 pH 7 附近容易获得或失去质子，因此常出现在酶活性位点中，在催化过程中给出或接受质子，同时还能帮助蛋白质缓冲小幅 pH 变化。
8. Negatively Charged (Acidic) R Groups | 带负电（酸性）R 基团
Aspartate (aspartic acid) and glutamate (glutamic acid) have side chains ending in a carboxyl group. At pH 7 this group is deprotonated to –COO⁻, giving the residue a negative charge.
天冬氨酸和谷氨酸的侧链末端带有一个羧基。在 pH 7 时，该基团去质子化为 –COO⁻，使残基带负电。
Like the basic residues, acidic residues are strongly hydrophilic and are almost always found on the solvent-exposed surface of a protein. They form salt bridges with lysine, arginine and histidine, and they can also coordinate metal ions such as Mg²⁺, Zn²⁺ and Ca²⁺.
与碱性残基一样，酸性残基亲水性很强，几乎总是位于蛋白质暴露于溶剂的表面。它们可与赖氨酸、精氨酸和组氨酸形成盐桥，还能配位 Mg²⁺、Zn²⁺、Ca²⁺ 等金属离子。
Glutamate is the residue that is mutated in sickle-cell anaemia. A single replacement of a charged, hydrophilic glutamate by a non-polar valine creates a hydrophobic patch on the surface of haemoglobin, causing the molecules to stick together and distort the red blood cell.
谷氨酸正是镰状细胞贫血症中发生突变的残基。一个带电荷、亲水的谷氨酸被非极性的缬氨酸取代，在血红蛋白表面形成疏水斑块，使分子相互黏附，从而让红细胞变形。
9. Special Cases: Glycine, Proline and Cysteine | 特例：甘氨酸、脯氨酸和半胱氨酸
Three amino acids break the general pattern and are worth memorising separately.
有三个氨基酸不符合一般规律，值得单独记忆。
Glycine | 甘氨酸: its R group is only a hydrogen atom, so it is the smallest amino acid. It is highly flexible and is often found in tight turns of a polypeptide chain.
Proline | 脯氨酸: its side chain loops back and bonds to the amino nitrogen, forming a rigid ring. This restricts rotation, so proline introduces a kink in a polypeptide chain and is rarely found inside an α-helix.
Cysteine | 半胱氨酸: it carries a sulfhydryl group (–SH). Two cysteine residues that are close together in a folded chain can be oxidised to form a covalent disulfide bridge (–S–S–).
Disulfide bridges are strong covalent bonds, so they hold the tertiary structure together far more firmly than hydrogen bonds or ionic bonds. They are especially common in secreted proteins such as insulin and antibodies, which must survive harsh conditions outside the cell.
二硫键是强共价键，因此它维持三级结构的能力远强于氢键或离子键。它在胰岛素、抗体等分泌型蛋白中特别常见，因为这类蛋白必须在细胞外的苛刻环境中保持稳定。
10. R Groups and Protein Folding | R 基团与蛋白质折叠
α-helix and the β-pleated sheet are held together by hydrogen bonds between the C=O and N–H groups of the polypeptide backbone - the R groups are not involved.
必须把主链的作用与 R 基团的作用区分开来。α-螺旋和 β-折叠是由多肽主链上 C=O 与 N–H 之间的氢键维持的，R 基团并不参与其中。
Once the chain begins to fold, however, the R groups take over. Non-polar side chains cluster in the interior to escape water, forming the hydrophobic core, while polar and charged side chains remain on the outside, where they can hydrogen-bond with water.
然而，一旦肽链开始折叠，R 基团便接管主导作用。非极性侧链为了避开水而聚集在内部，形成疏水核心；极性和带电侧链则留在外部，与水形成氢键。
Four types of R-group interaction then lock the tertiary structure in place:
随后，四类 R 基团相互作用把三级结构锁定就位：
Hydrogen bonds | 氢键: between polar side chains such as –OH and –CONH₂ groups.
Ionic bonds (salt bridges) | 离子键（盐桥）: between –NH₃⁺ and –COO⁻ side chains.
Hydrophobic interactions and van der Waals forces | 疏水相互作用与范德华力: between non-polar side chains buried in the core.
Disulfide bridges | 二硫键: strong covalent –S–S– links between cysteine residues.
Because most of these interactions are weak individually, the folded shape is only marginally stable. Heating or changing pH breaks the ionic and hydrogen bonds, and the protein unfolds - a process called denaturation.
由于这些相互作用单个来说大多很弱，折叠形状的稳定性其实相当有限。加热或改变 pH 会破坏离子键和氢键，蛋白质随之展开，这一过程称为变性。
11. R Groups, Enzymes and Binding Sites | R 基团、酶与结合位点
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