Inhoud
HC-01 31-08-2020 Intro + the basis........................................................................................................2
HC-02 (03-09-2020) Basics and Protein structure...................................................................................3
HC-03 (07-09-2020) Protein structure + protein function......................................................................6
WG-01 (09-09-2020) Flipped-Classroom................................................................................................8
HC-04 (09-09-2020) Protein Function + Control.....................................................................................8
HC-05 (11-09-2020) Protein dynamics..................................................................................................11
HC-06 (14-09-2020) Protein expression................................................................................................15
Work discussion 2 (16-09-2020)...........................................................................................................18
HC-07 (17-09-2020) Protein interaction...............................................................................................18
HC-08 (18-09-2020) Selected methods.................................................................................................21
HC-09 (21-09-2020) Protein engineering..............................................................................................24
HC-10 (24-09-2020) Tight junction proteins.........................................................................................25
HC-11 (25-09-2020) Antibiotic resistance.............................................................................................29
HC-12 (01-10-2020) New Antibacterials...............................................................................................33
HC-13 (05-10-2020) Molecular dynamics.............................................................................................34
HC-14 (08-10-2020) Hydrophobicity and effect on protein folding......................................................35
,HC-01 31-08-2020 Intro + the basis
Do not focus on names, facts and details, aim on understanding
Focus on main strategy in papers
One open question exam
The basics
Relevant elements:
- Atoms: nucleus with cloud of electrons orbiting around the nucleus. Differ by the number of
positive charged protons in the nucleus and an equal number of negative charged electrons
- Molecules: atoms connect by covalent bonds by sharing a pair of electrons. By sharing
electrons, atoms strive to get their outermost orbitals filled.
- In double bonds, four instead of two electrons are shared, this has consequences for
physical properties like free rotation impossibility around double bonds.
- Carbon: most abundant element in biology, grey/black color. Carbon has 4 electrons in outer
shell, so has to acquire or loose 4 electrons. Tetrahedral orientation. If carbon binds to 4
different elements, asymmetry dictates existence of stereo isomers, the L- or D-form of the
carbon element (differ in biological properties). Aminoacids are often L-form carbon. Carbon
can form really stron covalent bonds with other carbon atoms (chains, rings, branches)
- Nitrogen: second most abundant element in biology, green or blue color. Has 5 electrons in
outer shell, must accept 3 electrons. Can form amide bonds.
- Oxygen: 9% of our body dry mass. Red or darkblue color. 2 electrons missing in its outer
shell, it mostly accepts 2 electrons to form 2 bonds. CO compounds are building block,
functional groups, broad variety of structures can be made.
- Hydrogen: 1 electron in shell, it can gain or loose one. Acids release H, bases take up H.
Nitrogen containing molecules take up H. Protonation or deprotonation
Electronegativity:
- Shared electrons can be located more to one of the two atoms. Electronegativity is the ability
to attract electrons within a covalent bond. Left to right and bottom to top electronegativity
increases in the periodic table.
- Differences in electronegativity can invoke polarity when there is uneven charge distribution
within molecules. Oxygen in water gets a negative partial charge (electrons more near O),
hydrogen a positive partial charge (indicated by delta)
- Ionic bonds: electron transfers all the way one atom gains a electron, the other looses a
electron which makes a full negative charge on the one that gained the electron. Number
between 0-4, more that 1,7 difference is ionic bond.
pH value: quantify concentration of hydronium ions. -log of concentration of hydronium ions = pH
pKa value: chance that a group acquires or looses protons. pKa value indicates at which pH a
compound is half protonated. Strong OVERNEMEN pKa is -logpK
Interactions between chemical groups:
- Noncovalent:
- short range repulsions: occur upon narrowing distance between atoms, as e- orbitals
start to overlap the pauli principle starts to rule. First negative energy (system
releases energy) occurs, then positive energy (we have to put in energy). Then we
can hardly put them together. Distance at which atoms cannot get closer (there is
repulsion, you cannot compress the system more, is the sum of van der Waals radii.
London forces. Amstrom measure for radii of atoms, hydrogen is smallest. Atoms are
visualized as balls with impenetrable volume defined by vdW radius.
, - Electrostatic forces: point
charges: negative charges
repel and positive charges
repel eachother, larger
distance means lower
input/interaction energy.
deltaE is interaction energy.
Get idea in which direction
de interaction energy
changes when one of the
aspects changes.
- Electrostatic forces: dipoles: dipole moment equals the product of magnitude of the
charge times separation distance. Different electron attraction leads to dipoles.
Permanent (attractive or repulsive forces dependent on spatial arrangement) or
induced (due to forces originating from neighbouring permanent dipole, always
attractive, groups that usually do not dipole form dipole due to nearby dipole)
dipoles.
Electrons are always moving which makes that non dipoles sometimes have
spontaneous dipoles. Two spontaneous dipoles. The second molecule get
weak repulsion between electrons and then gets dipole too. UITZOEKEN
dispersion forces/London forces. Very small energy, but lots add up.
- Van der Waals interactions:
- Hydrogen bonds: they occur as two electronegative atoms compete for the same
hydrogen atom. Water is often involved and many amino acid side chains are
potentially involved.
- Hydrophobic effects
HC-02 (03-09-2020) Basics and Protein structure
Van der Waals interaction = Dispersion forces, sponanaous dipoles
Hydrophobic effect: forces nonpolar solutes to interact.
- Thermodynamics: can It occur spontaneously, H
is enthalpy (difference in energy of the old vs
new chemical bonds, energy set free – when
newly formed bonds are stronger), S is entropy
(temperature involved, probability)
- 2e law of thermodynamics: delta S is always
positive when reactions occur.
- This is called Gibbs free energy.
- Nonpolar molecules prefer nonpolar
environments.
- Hydrophobic solutes (non-polar) form droplets to minimize
surface. A cage like structure from water forms around the big
droplet, so less water molecules are in a less entropy situation.
Mole = 6022*10^23 particles (avogadro)
Molar = 1 mol/L
Equilibrium and rate
constants:
, Small deltaG changes will create major Keq changes
Noncovalent bonds: not a full charge, dipoles, small
energy. covalent bonds: charge separated, high energy
Protein structure
Protein structure levels:
- typical protein: 5nm, globular, 40000Da, 300 amino acid residues
- primary structure: linear sequence of amino acids in polypeptide
- secondary structure: beta sheets or alpha helix
- tertiary structure: 3-D Arrangement of sheets, helices, etc
- Quarternary Structure: Association of several polypeptides
Amino acids:
- Hydrogem, carbon, nitrogen, oxygen. Order of electronegativity: ONCH
- Some aminoacids are hydrophobic (in the center folded for cytosol proteins) and others are
hydrophilic, polar and thus charged (on the protein surface). Keep special structures in mind
(like the biggest or smallest or SH)
- Shown N->C
Peptide bond:
- Water splits and aminoacids form pair. Proteins are polypeptides of typically 100 aminoacid
residues
How to build specific structure?
- Covalent bonds make up the backbone
- Non-covalent bonds contribute to structure formation
- Helixes or betasheets with hydrogen bonds (noncovalent)
Secondary structure: alpha helix
- Stabilized by H-bonds of the peptide back-bone
- Right-handed
- Residues point to the outside
- H-CO
- 3.6aa per turn
Secondary structure: beta sheets:
- Hydrogen bonds
- Several beta strands make a beta sheet
- Antiparallell sheet: CO-NH bonds, straight bonds
HC-01 31-08-2020 Intro + the basis........................................................................................................2
HC-02 (03-09-2020) Basics and Protein structure...................................................................................3
HC-03 (07-09-2020) Protein structure + protein function......................................................................6
WG-01 (09-09-2020) Flipped-Classroom................................................................................................8
HC-04 (09-09-2020) Protein Function + Control.....................................................................................8
HC-05 (11-09-2020) Protein dynamics..................................................................................................11
HC-06 (14-09-2020) Protein expression................................................................................................15
Work discussion 2 (16-09-2020)...........................................................................................................18
HC-07 (17-09-2020) Protein interaction...............................................................................................18
HC-08 (18-09-2020) Selected methods.................................................................................................21
HC-09 (21-09-2020) Protein engineering..............................................................................................24
HC-10 (24-09-2020) Tight junction proteins.........................................................................................25
HC-11 (25-09-2020) Antibiotic resistance.............................................................................................29
HC-12 (01-10-2020) New Antibacterials...............................................................................................33
HC-13 (05-10-2020) Molecular dynamics.............................................................................................34
HC-14 (08-10-2020) Hydrophobicity and effect on protein folding......................................................35
,HC-01 31-08-2020 Intro + the basis
Do not focus on names, facts and details, aim on understanding
Focus on main strategy in papers
One open question exam
The basics
Relevant elements:
- Atoms: nucleus with cloud of electrons orbiting around the nucleus. Differ by the number of
positive charged protons in the nucleus and an equal number of negative charged electrons
- Molecules: atoms connect by covalent bonds by sharing a pair of electrons. By sharing
electrons, atoms strive to get their outermost orbitals filled.
- In double bonds, four instead of two electrons are shared, this has consequences for
physical properties like free rotation impossibility around double bonds.
- Carbon: most abundant element in biology, grey/black color. Carbon has 4 electrons in outer
shell, so has to acquire or loose 4 electrons. Tetrahedral orientation. If carbon binds to 4
different elements, asymmetry dictates existence of stereo isomers, the L- or D-form of the
carbon element (differ in biological properties). Aminoacids are often L-form carbon. Carbon
can form really stron covalent bonds with other carbon atoms (chains, rings, branches)
- Nitrogen: second most abundant element in biology, green or blue color. Has 5 electrons in
outer shell, must accept 3 electrons. Can form amide bonds.
- Oxygen: 9% of our body dry mass. Red or darkblue color. 2 electrons missing in its outer
shell, it mostly accepts 2 electrons to form 2 bonds. CO compounds are building block,
functional groups, broad variety of structures can be made.
- Hydrogen: 1 electron in shell, it can gain or loose one. Acids release H, bases take up H.
Nitrogen containing molecules take up H. Protonation or deprotonation
Electronegativity:
- Shared electrons can be located more to one of the two atoms. Electronegativity is the ability
to attract electrons within a covalent bond. Left to right and bottom to top electronegativity
increases in the periodic table.
- Differences in electronegativity can invoke polarity when there is uneven charge distribution
within molecules. Oxygen in water gets a negative partial charge (electrons more near O),
hydrogen a positive partial charge (indicated by delta)
- Ionic bonds: electron transfers all the way one atom gains a electron, the other looses a
electron which makes a full negative charge on the one that gained the electron. Number
between 0-4, more that 1,7 difference is ionic bond.
pH value: quantify concentration of hydronium ions. -log of concentration of hydronium ions = pH
pKa value: chance that a group acquires or looses protons. pKa value indicates at which pH a
compound is half protonated. Strong OVERNEMEN pKa is -logpK
Interactions between chemical groups:
- Noncovalent:
- short range repulsions: occur upon narrowing distance between atoms, as e- orbitals
start to overlap the pauli principle starts to rule. First negative energy (system
releases energy) occurs, then positive energy (we have to put in energy). Then we
can hardly put them together. Distance at which atoms cannot get closer (there is
repulsion, you cannot compress the system more, is the sum of van der Waals radii.
London forces. Amstrom measure for radii of atoms, hydrogen is smallest. Atoms are
visualized as balls with impenetrable volume defined by vdW radius.
, - Electrostatic forces: point
charges: negative charges
repel and positive charges
repel eachother, larger
distance means lower
input/interaction energy.
deltaE is interaction energy.
Get idea in which direction
de interaction energy
changes when one of the
aspects changes.
- Electrostatic forces: dipoles: dipole moment equals the product of magnitude of the
charge times separation distance. Different electron attraction leads to dipoles.
Permanent (attractive or repulsive forces dependent on spatial arrangement) or
induced (due to forces originating from neighbouring permanent dipole, always
attractive, groups that usually do not dipole form dipole due to nearby dipole)
dipoles.
Electrons are always moving which makes that non dipoles sometimes have
spontaneous dipoles. Two spontaneous dipoles. The second molecule get
weak repulsion between electrons and then gets dipole too. UITZOEKEN
dispersion forces/London forces. Very small energy, but lots add up.
- Van der Waals interactions:
- Hydrogen bonds: they occur as two electronegative atoms compete for the same
hydrogen atom. Water is often involved and many amino acid side chains are
potentially involved.
- Hydrophobic effects
HC-02 (03-09-2020) Basics and Protein structure
Van der Waals interaction = Dispersion forces, sponanaous dipoles
Hydrophobic effect: forces nonpolar solutes to interact.
- Thermodynamics: can It occur spontaneously, H
is enthalpy (difference in energy of the old vs
new chemical bonds, energy set free – when
newly formed bonds are stronger), S is entropy
(temperature involved, probability)
- 2e law of thermodynamics: delta S is always
positive when reactions occur.
- This is called Gibbs free energy.
- Nonpolar molecules prefer nonpolar
environments.
- Hydrophobic solutes (non-polar) form droplets to minimize
surface. A cage like structure from water forms around the big
droplet, so less water molecules are in a less entropy situation.
Mole = 6022*10^23 particles (avogadro)
Molar = 1 mol/L
Equilibrium and rate
constants:
, Small deltaG changes will create major Keq changes
Noncovalent bonds: not a full charge, dipoles, small
energy. covalent bonds: charge separated, high energy
Protein structure
Protein structure levels:
- typical protein: 5nm, globular, 40000Da, 300 amino acid residues
- primary structure: linear sequence of amino acids in polypeptide
- secondary structure: beta sheets or alpha helix
- tertiary structure: 3-D Arrangement of sheets, helices, etc
- Quarternary Structure: Association of several polypeptides
Amino acids:
- Hydrogem, carbon, nitrogen, oxygen. Order of electronegativity: ONCH
- Some aminoacids are hydrophobic (in the center folded for cytosol proteins) and others are
hydrophilic, polar and thus charged (on the protein surface). Keep special structures in mind
(like the biggest or smallest or SH)
- Shown N->C
Peptide bond:
- Water splits and aminoacids form pair. Proteins are polypeptides of typically 100 aminoacid
residues
How to build specific structure?
- Covalent bonds make up the backbone
- Non-covalent bonds contribute to structure formation
- Helixes or betasheets with hydrogen bonds (noncovalent)
Secondary structure: alpha helix
- Stabilized by H-bonds of the peptide back-bone
- Right-handed
- Residues point to the outside
- H-CO
- 3.6aa per turn
Secondary structure: beta sheets:
- Hydrogen bonds
- Several beta strands make a beta sheet
- Antiparallell sheet: CO-NH bonds, straight bonds
