H3 MOLECULAR BIOLOGY
BIOCHEMICAL AND BIOPHYSICAL PRINCIPLES
Non-covalent interactions (intermolecular forces)
● Stability
○ Biomacromolecules can fold into a 3D structure and form complexes and
assemblies, stabilised by non-covalent interactions
○ Magnitude of non-covalent interactions must be greater than that of the thermal
energy of the molecule (chaotic vibrational, rotational and translational motions) in
order for it to be stable
● Electrostatic charge-charge interactions
○ Governed by Coulomb’s law
|F| = k(q1q2)/(εr2)
where q1 and q2 are the signed magnitudes of the charges, r is the distance between the charges, ε
is the dielectric constant of the medium and k = 1/(4πε0) (ε0 is the electric constant)
○ Energy of interaction (U)
U = k(q1q2)/(εr)
where q1 and q2 are the signed magnitudes of the charges, r is the distance between the charges, ε
is the dielectric constant of the medium and k = 1/(4πε0) (ε0 is the electric constant)
● London dispersion forces
○ The motion of the electrons in a particle at any instantaneous moment is
synchronized so that each particle has a distorted electron distribution giving a
momentary dipole moment
○ These dipoles are directed to give an attractive force between the particles
● Hydrogen bond
○ Formed between a H bound to a more electronegative atom (N/O/F) and another
electronegative atom (N/O/F)
Hydrophobic effect
● Tendency for nonpolar substances to aggregate in an aqueous solution and exclude water
molecules
○ Nonpolar substance when dissolved in water is surrounded by a “clathrate cage” of
associated water molecules -> lowers entropy and hence is less favourable
○ More favourable for nonpolar substance to self-associate to a separate phase rather
than dissolve in water
Amphipathic molecules
● Formation of aggregates (due to hydrophobic effect)
○ Micelle -> hexagonal cylindrical -> lamellar (decreasing water content)
○ Phospholipids are cylindrical and mainly form bilayers (lamellar structures); fatty
acids are more cone-like and form micelles at high water content
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, PROTEIN STRUCTURE
Secondary structure
α-helix
● Hydrogen bonding between carbonyl group of 1 residue (i) and amino group of another
residue 4 units away in the same chain (i+4)
● Right-handed coil (3.6 amino acids per turn)
310 helix
● Hydrogen bonding between carbonyl group of 1 residue (i) and amino group of another
residue 3 units away in the same chain (i+3)
● Right-handed coil (3 amino acids per turn)
● Typically observed at the end of α-helices
π-helix
● Hydrogen bonding between carbonyl group of 1 residue (i) and amino group of another
residue 5 units away in the same chain (i+5)
● Right-handed coil (4.1 amino acids per turn)
● Typically short in length (7 to 10 residues) and are almost always associated with (i.e.
flanked by) α-helices on either end
β-sheet
● 2 or more amino acid sequences (β-strands) arranged adjacently in parallel/antiparallel
conformation
● Hydrogen bonds between carbonyl group of 1 residue on one sequence and amino group of
another residue on a parallel/antiparallel sequence
β-turn
● Involves 4 amino acid residues
● Hydrogen bond between carbonyl group of residue i and amino group of residue i+3
● Type I (most common) and type II: distinguished by the Φ/ψ angles of residues i+1 and i+2
● Usually found between 2 α-helices, 2 β-sheets, or 1 α-helix and 1 β-sheet
β-hairpin (structural motif)
● Involves two beta strands that look like a hairpin
● Two adjacent antiparallel strands linked by a short loop of
two to five amino acids
Ω-loop (structural motif)
● Loop of 6-16 residues
● Connects 2 α-helices, 2 β-sheets, or 1 α-helix and 1 β-sheet
Copyright © 2019 tonyndr
, NUCLEIC ACID STRUCTURE
Forms of DNA (that are biologically active)
● B-form (most common)
● A-form
● Z-form
Copyright © 2019 tonyndr
BIOCHEMICAL AND BIOPHYSICAL PRINCIPLES
Non-covalent interactions (intermolecular forces)
● Stability
○ Biomacromolecules can fold into a 3D structure and form complexes and
assemblies, stabilised by non-covalent interactions
○ Magnitude of non-covalent interactions must be greater than that of the thermal
energy of the molecule (chaotic vibrational, rotational and translational motions) in
order for it to be stable
● Electrostatic charge-charge interactions
○ Governed by Coulomb’s law
|F| = k(q1q2)/(εr2)
where q1 and q2 are the signed magnitudes of the charges, r is the distance between the charges, ε
is the dielectric constant of the medium and k = 1/(4πε0) (ε0 is the electric constant)
○ Energy of interaction (U)
U = k(q1q2)/(εr)
where q1 and q2 are the signed magnitudes of the charges, r is the distance between the charges, ε
is the dielectric constant of the medium and k = 1/(4πε0) (ε0 is the electric constant)
● London dispersion forces
○ The motion of the electrons in a particle at any instantaneous moment is
synchronized so that each particle has a distorted electron distribution giving a
momentary dipole moment
○ These dipoles are directed to give an attractive force between the particles
● Hydrogen bond
○ Formed between a H bound to a more electronegative atom (N/O/F) and another
electronegative atom (N/O/F)
Hydrophobic effect
● Tendency for nonpolar substances to aggregate in an aqueous solution and exclude water
molecules
○ Nonpolar substance when dissolved in water is surrounded by a “clathrate cage” of
associated water molecules -> lowers entropy and hence is less favourable
○ More favourable for nonpolar substance to self-associate to a separate phase rather
than dissolve in water
Amphipathic molecules
● Formation of aggregates (due to hydrophobic effect)
○ Micelle -> hexagonal cylindrical -> lamellar (decreasing water content)
○ Phospholipids are cylindrical and mainly form bilayers (lamellar structures); fatty
acids are more cone-like and form micelles at high water content
Copyright © 2019 tonyndr
, PROTEIN STRUCTURE
Secondary structure
α-helix
● Hydrogen bonding between carbonyl group of 1 residue (i) and amino group of another
residue 4 units away in the same chain (i+4)
● Right-handed coil (3.6 amino acids per turn)
310 helix
● Hydrogen bonding between carbonyl group of 1 residue (i) and amino group of another
residue 3 units away in the same chain (i+3)
● Right-handed coil (3 amino acids per turn)
● Typically observed at the end of α-helices
π-helix
● Hydrogen bonding between carbonyl group of 1 residue (i) and amino group of another
residue 5 units away in the same chain (i+5)
● Right-handed coil (4.1 amino acids per turn)
● Typically short in length (7 to 10 residues) and are almost always associated with (i.e.
flanked by) α-helices on either end
β-sheet
● 2 or more amino acid sequences (β-strands) arranged adjacently in parallel/antiparallel
conformation
● Hydrogen bonds between carbonyl group of 1 residue on one sequence and amino group of
another residue on a parallel/antiparallel sequence
β-turn
● Involves 4 amino acid residues
● Hydrogen bond between carbonyl group of residue i and amino group of residue i+3
● Type I (most common) and type II: distinguished by the Φ/ψ angles of residues i+1 and i+2
● Usually found between 2 α-helices, 2 β-sheets, or 1 α-helix and 1 β-sheet
β-hairpin (structural motif)
● Involves two beta strands that look like a hairpin
● Two adjacent antiparallel strands linked by a short loop of
two to five amino acids
Ω-loop (structural motif)
● Loop of 6-16 residues
● Connects 2 α-helices, 2 β-sheets, or 1 α-helix and 1 β-sheet
Copyright © 2019 tonyndr
, NUCLEIC ACID STRUCTURE
Forms of DNA (that are biologically active)
● B-form (most common)
● A-form
● Z-form
Copyright © 2019 tonyndr
