Biochemical Terminology & Non-Covalent Interctions

Lecture 1

Biochemical hierarchy

organizational level of biological systems from simplest to most complex

Most Abundant Elements in Organic Matter (6)

>97% weight

CHNOPS (Carbon, Hydrogen Nitrogen, Oxygen, Phosphorous. Sulfur)

Common chemical/functional groups (6)

amino (-NH₃)

hydroxyl (-OH)

sulfhydryl (-SH)

phosphoryl (-PO₃^2-)

carboxyl (-COO)

methyl (-CH₃)

major classes of biomolecules (4)

amino acids

nucleotides

simple sugars

fatty acids

Macromolecules

polymers made up of small molecules

ex. nucleic acids, polysaccharides, proteins

Central Dogma

flow of information in a biological pathway

DNA → RNA → proteins

structure-function relationships

Sequence of polymer → 3D structure → function

Crowding

biochemical systems are packed tightly together

Effective macromolecular concentration in cytoplasm ~300-400 mg/mL

non-covalent interactions

important for the formation of biomolecular structures

Intermolecular interactions

within the same molecule

Intramolecular interactions

between more than one molecule

Covalent bonds

connecting the atoms that form macromolecules; stronger than non-covalent interactions

non-covalent interactions

dictates stability/function of the 3-D architecture of macromolecules

Are Non-Covalent Interactions stronger or weaker than covalent bonds?

weaker; individually weak but together strong

WHy does nature often rely on Non-Covalent Interactions?

facilitate transient and reversible interactions

Bond energies

describe energy used to break a bond for released to form a bond

Hydrogen bonds

attractive interaction between hydrogen and electronegative atoms (FON); dipole-dipole interaction that depends on distance and direction (preferred 180°); essential in forming biomolecular structures

electrostatic/ion-pairs/salt bridges

interaction between two ions close to each other; governed by Coulomb’s Law; most stable non-covalent interaction

Van der Waals force

force between neutral atoms based on distance; weak

types of non-covalent interactions

1. Hydrogen bonds

2. Ion-pairs (salt bridges)

3. Van der Waals force

4. Aromatic interactions

5. Hydrophobic effect

dipoles

separation of positive and negative charges in a molecule; can be caused by a redistribution of electron density

dipole moment

sum of the difference in electronegativity over the molecule; depends on atom electronegativity and orientation

induced dipole interactions

occur due to transient fluctuation in electron clouds which set up transient dipoles, which mutually reinforce each other

electron repulsion

limits the vicinity of two atoms

Van der Waals radius (r_vdw)

radius of the “hard sphere:; half the distance between closest approach of two nonbonded atoms of a given element; limited by electric repulsion; Atoms interact optimally when the distance between them is equal to the sum of their r_vdw

optimal distance

preferred distance for two atoms to interact; equal to the sum of their r_vdw

steric effect

Repulsion between atoms at short distances; constrains the 3-D structures of biomolecules

stabilization energy

minimum in ATOMIC INTERACTION graph; when two atoms are in van der Waals contact

shielding

The environment/medium that an ion pair is in can weaken electrostatic interactions

electric permittivity (ε)

influences how charges move across a medium; influences strength of electrostatic interaction

π-stacking

derive from dipole/dipole interaction; pi bonds are more polarizable than sigma bonds; positively charged regions interact favorably with negatively charged areas above/below

energy between two molecules

estimated based on additive pairwise non-covalent interactions; approximate b/c doesn’t include three-body effects