structure and function Flashcards
What are electrostatic interactions
ionic interaction between groups carrying opposite charge
Strength of interaction is dependent on pH and salt concentration, and inversely proportional to distance between partners.
Hydrophobic environment more favourable
Often important for initial binding
what is hydrogen bonding
interaction between an electron rich atom and electron deficient hydrogen atom.
the electron deficient hydrogen is covalently bonded to an electronegative atom, inducing a partial positive charge on hydrogen.
Also involves orbital overlap
what can increase a hydrogen bond acceptors ability to accept electrons?
what limits its ability?
increasing the electron density
Limits the ability - delocalisation of electrons
hydrogen bond acceptor strengths for: tertiary amine, amide, aniline
Teritary amine - good HBA
Amide - poor because electron density is with the O not the N
Aniline - poor as the lone pairs can delocalise so they’re not available
what can increase a protons ability to HBD?
the more electron deficient it is the better
what are Van Der waals forces?
London forces - weak forces but the sum of the forces add up to a significant effect
Occurs in hydrophobic regions
Electron density is spread out in these regions
what is a dipole dipole interaction?
polarisation of a bond by presence of an electronegative atom produces a permanent dipole.
- Permanent dipole moments have an associated direction
- correct orientation of dipoles will result in a stronger interaction and drug binding affinity (if direction is wrong then can bind)
Ion dipole interaction
interaction of the permanent dipole of one molecular with the ionic charge on the other.
What is the role of water?
drugs exist in aqueous environment and are solvated by water molecules.
Water molecules can interfere with binding interactions
Polar groups are useful for solubility of drug molecules in aqueous environments
We need to position groups properly so to avoid solvation energy penalty
explain hydrophobic interactions
non polar regions can increase stability through expulsion of water between adjacent regions.
Water can’t solvate non polar so form ordered structures around them- thus the entropy has decreased.
Binding of a drug frees a water molecule to become less ordered and results in an increase in binding energy
explain repulsive interactions
need to have these in order to prevent the molecules staying in the binding site - when molecules come in close contact, orbital overlap occurs leading to repulsion. 2 identically charged molecules will repel each other
explain intermolecular interactions
order of intensity over a distance is important for these interactions.
- electrostatic (inversely proportional to distance)
- Ion dipole
- Dipole-dipole
- VDW
electrostatic and ion dipole important for initial attraction
dipole dipole, hydrogen bonding & VDW hold molecule once in position
what are enzymes?
proteins that catalyse chemical reactions. They lower the activation energy and provide a reaction surface and environment.
Position the reactants in an optimum position for a reaction to occur
weaken bonds
what is the active site?
Site at which molecule binds.
Must be near the surface to allow access
Often hydrophobic nature to facilitate reactions that are unlikely to occur in aqueous environment
Amino acids in the active site are important - for binding and catalysing
what is the theory of induced fit?
changes in shape are driven by maximisation of intermolecular binding interactions.
Explains how a range of substrates are tolerated by the enzyme. Bond rotation can occur to fix the enzyme in a different conformation. Substrate is then held in position for a reaction to occur.
binding interaction must be strong enough to hold substrate but must allow the release of products.
