Question

• Discuss covalent, ionic, hydrophobic and vanderwaals forces in a tertiary structure of a protein. Discuss or define Atomic structure, hydrogen bonding and how it affects the mechanical and chemical properties of water. What are some features of hydrocarbons, Geometric isomers, structural isomers and Enantiomers? What are the three levels of protein structure, discuss the bonds involved?

Answer 1

Tertiary structure of a protein refers to the three-dimensional structure of an entire polypeptide (consisting of amino acids), including its side chains. The forces that give rise to a tertiary structure largely involve covalent and non-covalent bonds.

Tertiary structure is held together by four different bonds and interactions:

• Ionic Bonds - If two oppositely charged ‘R’ groups (+ve and -ve) are found close to each other, and ionic bond forms between them. Some amino acids (such as aspartic acid and glutamic acid) contain an extra -COOH group. Some amino acids (such as lysine) contain an extra -NH₂ group. A hydrogen ion from the -COOH can be transferred to the -NH₂ group to form zwitterions just as in simple amino acids to get an ionic bond between the negative and the positive group if the chains folded in such a way that they were close to each other.
• Hydrogen Bonds - Lots of amino acids contain groups in the side chains which have a hydrogen atom attached to either an oxygen or a nitrogen atom, where Hydrogen bonding can occur. For example, the amino acid serine contains an -OH group in the side chain. A hydrogen bond can form between two serine residues in different parts of a folded chain.
• Disulphide Bonds - Where two Cysteine amino acids are found together, a strong double bond (S=S) is formed between the Sulphur atoms within the Cysteine monomers.
• Hydrophobic and Hydrophilic Interactions - Some amino acids may be hydrophobic while others are hydrophilic. In a water based environment, a globular protein will orientate itself such that it’s hydrophobic parts are towards its center and its hydrophilic parts are towards its edges. Several amino acids have quite large hydrocarbon groups in their side chains. Temporary fluctuating dipoles in one of these groups could induce opposite dipoles in another group on a nearby folded chain. The dispersion forces set up would be enough to hold the folded structure together by vanderwall interactions.

All these forces work together to form a whole complex tertiary protein structure which involved the secondary beta sheets and alpha helices.

Atomic structure of Water molecule: A water molecule consists of two hydrogen atoms bonded to an oxygen atom. The O-O-H bond distance is 0.958 Å, and the angle formed by the three atoms is 104.5. The hydrogen atoms are not arranged linearly, because the oxygen atom’s hybrid orbitals (sp3) extend roughly toward the corners of a tetrahedron. Hydrogen atoms occupy two corners of the tetrahedron, and the non-bonding electron pairs of the oxygen atom occupy the other two corners.

Water Molecules Form Hydrogen Bonds:  Water is a polar molecule. The oxygen atom has un-shared electrons which carries a partial negative charge and the hydrogen atoms each carry a partial positive charge.
Electrostatic attractions between the dipoles of water molecules are crucial in providing water its chemical and mechanical properties. Neighboring water molecules tend to orient themselves so that the OOH bond of one water molecule points toward one of the electron pairs of the other water molecule. The resulting association is known as a hydrogen bond.
Hydrogen bonds are structurally characterized by an distance that is at least 0.5 Å shorter than the calculated van der Waals
distance. A single water molecule contains two hydrogen atoms that can be donated and two unshared electron pairs that can act as acceptors, so each molecule can participate in a maximum of four hydrogen bonds with other water molecules.

Ice is formed due to the hydrogen bonds in water and provides a classic provides a striking example of the cumulative strength of many hydrogen bonds. Each water molecule is tetrahedrally surrounded by four nearest neighbors to which it is hydrogen bonded. As a consequence of its open structure, water is one of the very few substances that expands on
freezing.

Hydrocarbons: They are the simplest organic compounds and are made up of only Carbon and Hydrogen atoms only. They can be saturated (single bonds) or unsaturated double and triple bonds)

Enantiomers: Enantiomers are those isomers that are mirror images of each other. Eg, R and S-2 Chlorobutane

Proteins form four levels of structures:

Primary structure: Proteins are synthesized by a series of steps called transcription (the use of a DNA strand to make a complimentary messenger RNA strand - mRNA) and translation (the mRNA sequence is used as a template to guide the synthesis of the chain of amino acids which make up the protein). Often, post-translational modifications, such as glycosylation or phosphorylation, occur which are necessary for the biological function of the protein. The amino acid sequence makes up the primary structure of the protein, which are linked to each other in a straight chain.

Secondary structure: It is the local spatial arrangement of a polypeptide’s backbone atoms without regard to the conformations of its side chains.

The α-helix is a right-handed coiled strand. The side-chain substituents of the amino acid groups in an α-helix extend to the outside. Hydrogen bonds form between the oxygen of the C=O of each peptide bond in the strand and the hydrogen of the N-H group of the peptide bond four amino acids below it in the helix. The hydrogen bonds make this structure especially stable. The side-chain substituents of the amino acids fit in beside the N-H groups.

The hydrogen bonding in a ß-sheet is between strands (inter-strand) rather than within strands (intra-strand). The sheet conformation consists of pairs of strands lying side-by-side. The carbonyl oxygens in one strand hydrogen bond with the amino hydrogens of the adjacent strand. The two strands can be either parallel or anti-parallel depending on whether the strand directions (N-terminus to C-terminus) are the same or opposite. The anti-parallel ß-sheet is more stable due to the more well-aligned hydrogen bonds.

Tertiary structure refers to the three-dimensional structure of an entire polypeptide, including its side chains. The forces that give rise to a tertiary structure largely involve covalent and non-covalent bonds.

Many proteins are composed of two or more polypeptide chains, loosely referred to as subunits. A protein’s quaternary structure refers to the spatial arrangement of its subunits. The final shape of the protein complex is once again stabilized by various interactions, including hydrogen-bonding, disulfide-bridges and salt bridges.