Biophysics Flashcards
What are the names of the 3 types of cells that were made from a common ancestor several billion years ago (called domains)?
Bacteria, archaea and eukarya
Which two types of domain are very similar?
Bacteria and archaea
What determines the divisions of the domains/cell types?
The similarities and differences in ribosomal RNA sequences
What are the two types of cells?
Eukaryotic and prokaryotic
What is the main difference between eukaryotic and prokaryotic cells?
Eukaryotic cells have a nucleus that contain genetic material (DNA) and prokaryotic cells do not have a nucleus
Where are eukaryotic cells found?
In animals, plants, fungi, protozoa and algae
Are bacteria eukaryotic or prokaryotic?
Prokaryotic
Are eukaryotic organisms uni- or multi- cellular or either?
Either
Are prokaryotic organisms uni- or multi- cellular or either?
Always uni-cellular
What can cells do?
Regulate biochemical processes, control chemical flux between compartments, have structural integrity, exert forces and react dynamically
What are organelles and are they membrane bound?
They are compartments within a cell that have specific specialised functions and they can be membrane bound (made of lipids) or membraneless
Can organelle compartments have completely different protein and ion composition to compartments surrounding it?
Yes
What can the structural features of the interior of a eukaryotic cell be built from?
Lipids or proteins
What is the outside ‘fabric’ of the cell called and what is it made of?
Plasma membrane and its made of lipids
Name some organelles in eukaryotic cells
Nuclear membrane, the Golgi Apparatus, the Endoplasmic Reticulum and the Mitochondria
What are microtubules and actin filaments and what are they made of?
Structural features in eukaryotic cells (eg cell shape) and are made of proteins
What part of the cell contains the genome?
The nucleus
Does knowing the genome tell you anything about what an individual cells does or is doing?
No
What surrounds the nucleus and why does it contain pores?
The nuclear envelope/membrane and the pores allow messenger RNA diffusion in and out
What is the central dogma of cell biology?
The theory that genetic information flows only in one direction, from DNA, to RNA, to protein
How do cells regulate their function?
Controlling the concentration of various proteins
Do all the cells in the body contain the same DNA?
Yes
What is a phenotype and genotype?
The genotype is a set of genes in DNA responsible for unique trait or characteristics while the phenotype is the physical appearance or characteristic of an organism resulting from their genetic makeup
What causes the differences between types of cell?
The regulation of protein expression and degradation
What is a gene?
A short section of DNA that carries the information to make a molecule (usually a protein) and can vary in size
What is the genome?
The entire sequence of genes and bases
What is a chromosome and how many are there in a cell?
It is a tightly packed coiled of DNA and there are 23 pairs so 46 overall
What is a protein?
A large molecule made up of chains of amino acids, which are essential to the functioning of our cells
What are alleles in humans?
They are different forms of the same gene, one from our biological mother, one from our biological father so there is one on each chromosome
What are the main two classes of nucleic acids?
DNA and RNA
What is a nucleotide?
The basic building block of nucleic acids and consists of a sugar molecule (either ribose for RNA or deoxyribose for DNA) attached to a phosphate and a base
Why are DNA and RNA called nucleic acids?
They are acids and found in high concentration in the nucleus of the cells
Although DNA and RNA are very similar, what makes them different?
RNA is less stable and in shorter chains
What are the bases called?
Adenine (A), cytosine (C), guanine (G), thymine (T) (DNA only) and uracil (U) (RNA only)
What are the base pairs in DNA and RNA?
G with C for both, A with T for DNA and A with U for RNA
How long is a base pair roughly?
3.4 times 10 to the -10 metres
What does DNA look like?
Two strands intertwined into a helix, with the sugar-phosphate on the outside and the bases on the interior of the strand
RNA and DNA contain ribose sugars, how are the carbon atoms in the sugars numbered?
1’ to 5’
Why aren’t the carbon atoms shown on the diagrams for deoxyribose and ribose?
For clarity, but they are in fact on the corners
What is the difference between the ribose and deoxyribose sugars?
Ribose has a hydroxyl group (OH) on the 2’ carbon atom, whilst deoxyribose only has hydrogen on the 2’ carbon atom
Is ribose the same thing as d-ribose?
Yes
Where are the bases attached to each sugar?
At the 1’ carbon atom position
How are sugars linked in DNA and RNA to make the backbone of a strand?
Phosphodiester bridges
What is the phosphodiester bond?
It links the 3’ carbon atom of one sugar molecule to the 5’ carbon atom of another, which forms a repeating sugar-phosphate backbone
What element do all the bases include?
Nitrogen
What two bases are derivative of purine and which three bases are derivatives of pyrimidine?
A and G are derivatives of purine, whilst C, T and U are derivatives of pyrimidine
What is a codon?
A DNA or RNA sequence of 3 nucleotides which together form a unit of genetic code
What does it mean that the base sequences of nucleic acids are always written in the 5’ to 3’ direction?
Any single strand will have an unbound 5’ phosphate at one end and nucleotides are added only to the 3’ end of the growing strand. It is always read in the 5’ to 3’ direction
What direction are DNA and RNA synthesised in living cells?
5’ to 3’ direction
What is electronegativity?
It is the measure of the tendency of an atom to attract a bonding pair of electrons
What happens if an atom is more electronegative than another?
It will attract the electron pair more than the other atom, which means it has more than its fair share of electron density and becomes negative and the other atom positive, creating a dipole
What are hydrogen bonds?
A hydrogen atom covalently bonded to a very electronegative atom and another very electronegative atom with an available lone pair of electrons
How are the complementary base pairs on separate strands connected to one another?
Hydrogen bonds
Who and when was the double helix postulated?
Crick and Watson in 1953
What is Chargaff’s rule?
For any organism, the concentration of bases obey that A/T and C/G is approximately 1 but T/G varies widely
What does it mean that the two strands of DNA have complementary base sequences?
They carry the same information in different forms
If the strands in a double helix are separated, how can the original double helix be built from each one individually?
Templated polymerisation
What are the main differences between the DNA types?
The number of base pairs per turn of the helix, the tilt of the base pairs, the diameter of the helix and the nature of the grooves of the helix
What form of DNA is seen in nature?
B form
How many residues per turn of the axis does B form DNA have and how are they angled?
10 and they are virtually planar and perpendicular to the helix axis
What is the diameter of B form DNA and what is the nature of the grooves on it?
Around 2.2nm and the major groove is wider than the minor groove that are on opposite sides of the helix
Is A, B and Z form DNA right or left handed helices?
A and B are right, Z is left
What is the differences between A and B form DNA?
B form is wider and stubbier, with 11 residues per turn of the helix and a few angstroms wider in diameter. The bases make an angle of 20 degrees with the helix axis in B form but are also planar
What is the difference between Z form DNA and the other two types?
The major and minor grooves of the Z form DNA show little difference in width
What is chromatin?
The formed DNA double helix in the cell nucleus that is packaged by special proteins called histones is chromatin and is the material that chromosomes are made from
What is a nucleosome?
A nucleosome is the basic structural unit of DNA packaging in eukaryotes. It is a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundamental subunit of chromatin
How many amino acids are there and what are the other types of codons called?
20 and there are start and stop codons
What is replication?
It is when DNA makes a copy of itself
How does DNA replication happen?
The double helix unzips along its backbone with help from the DNA helicase, which leaves unpaired bases that free nucleotides in the nucleus match up with, with the help of an enzyme type called DNA polymerases and this leads to new strands of identical DNA
What is messenger RNA (mRNA)?
It reads information from the DNA and is involved in protein synthesis
What is transfer RNA (tRNA)?
It transfers specific amino acids onto a growing polypeptide sequence
What is micro RNA (miRNA) and small interefering RNA (siRNA)?
They break down mRNA or prevent it from going on to form proteins or can increase/ decrease the transcription of certain genes
What is DNA origami?
It is the process where a single long strand of DNA is folded into the desired shape by the placement of shorter, complementary staple strands
Why can DNA be used structurally to produce 2 and 3 dimensional shapes?
The specificity of the interactions between base pairs
What can DNA origami be used for?
Delivery systems (like a box with a lid)
What are viruses?
Nucleic acids wrapped up in a coating of protein to protect them and help them invade a cell
How do viruses function?
They insert their genome into yours, turning your cells into a factory for new virions (complete virus outside of a host cell)
What is a macromolecular assembly?
It is massive chemical structures that are complex mixtures of polypeptide (like proteins), polynucleotide (like nucleic acids), polysaccharides (like sugars) or other polymeric molecules
What are examples of macromolecular assemblies?
Viruses, cellular organelles, membranes and ribosomes
What are capsids and what shape are they often in?
They are protein assemblies on the surface of a virus and the shape is often an icosahedra
What are some additions to the basic structure of viruses?
Lipid envelope (HIV), surface receptors and internal molecular machines
What is a useful measure of the degree of DNA packing?
The ratio of the volume taken up by the DNA to the volume of the region where the DNA is stored
If we approximate the volume per base pair for DNA roughly 1nm cubed, and the volume of the region where DNA is stored is also in nm cubed, how can we simplify the DNA packing ratio?
The number of base pairs over the volume of the container
Is DNA densely packed in cells and viruses?
Yes (almost crystalline packing density in some cases)
What is the names of the processes from DNA to protein?
Replication, transcription and translation
What happens during transcription?
The DNA of a gene serves as a template for complementary base-pairing, and an enzyme called RNA polymerase helps the formation of a pre-mRNA molecule, which is then processed to form mature mRNA
What happens during translation?
The mRNA leaves the nucleus into the cytoplasm and goes to the ribosome. The mRNA is read with the help of tRNA. Each group of three bases in mRNA constitutes a codon, and each codon specifies a particular amino acid.
If the sequence of bases controls the structure of proteins, will the exact same sequence go into the same 3D folded shape or a different shape?
The exact same
What are enzymes?
They are proteins that are catalysts that control most biochemical proceses
What are the 4 levels of complexity in protein structure?
Primary, secondary, tertiary and quaternary
What structure do most proteins have?
Tertiary
Does the molecular weight change for the same type of protein?
No
What is Levinthal’s paradox?
Correct protein folding by a simple random search is vanishingly improbable but correctly folded proteins are common
What resolves Levinthal’s paradox?
Protein sequences contain information on folding paths as well as on the stability of the folded structure, it is not random folding
Do folded or unfolded proteins have more energy?
Unfolded
How many amino acid residues do polypeptide chains usually have?
Between 50 and 2000
What are oligopeptides (also known as just peptides)?
Shorter amino acid chains (<50)
What do we measure the mass of proteins in?
Daltons (Da)
What is the typical range of most proteins masses and what can it go up to?
5-200 kDa but can go up to 3600kDa
What is the primary structure of a protein?
The sequence of residues in the polypeptide chain and at the ends there are bare amino and carboxyl groups
What are the ends of a polypeptides labelled and how is the sequence of residues always written from?
N and C (for amino and carboxy groups) and they are written from N to C
Will the protein function if the primary structure isn’t correct?
No
What types of amino acids make up proteins and what atom are the amino groups and carboxyl groups attached to in this type?
Alpha-amino acids and carbon (called the alpha carbon atom)
What are zwitterions?
Molecules that carry charged groups of opposite polarity
What is the alpha carbon also linked with in the amino acid(aside from the amino and carboxyl groups)?
A hydrogen atom and a fourth group ‘R’, which is the side chain and this distinguishes one amino acid from another
What do amino acids contain?
An anime, carboxylic acid and a side chain
How are amino acids linked?
Acid to amine
What links together a peptide?
A peptide bond
Water is produced in the making of peptides, what does this make the reaction?
A dehydration reaction
Does the making of peptides happens on its own?
No, it’s enzyme-catalysed
What form are peptides in?
They are planar/flat
What are the two possible planar configuration of the peptide unit and what’s the most common?
Cis and trans related by 180 degrees rotation about the peptide bond. Trans is more common because in the cis one the side chains can clash
The backbone consists of planar peptide locked in trans configuration that are joined at what atoms?
Alpha carbon atoms
There are two degrees of freedom at each alpha carbon atom relating to rotation about the bonds to nitrogen and carbonyl carbon atoms, what are these angles restricted by?
Steric clashes (unnatural overlaps), including side chain clashes
What is a Ramachandran plot?
The plot between the angles of the two degrees of freedom for alpha carbon atoms and shaded areas represent allowed combinations with no to low clashes
What holds together secondary structures?
Hydrogen bonds
What accounts for the increase in entropy and decrease in enthalpy for secondary structures?
Entropy is due to the vast number of possible configurations of a random coil and decrease in enthalpy is due to a particularly favourable packing arrangement
What type of structure is the alpha helix?
Secondary
Describe the alpha helix
It is a right-handed, single helix formed from a single polypeptide chain with a tightly packed backbone on the inside and side chains that project outwards to avoid clashes
What are beta pleated sheets formed from?
Extended polypeptide strands running alongside each other and held together by interstrand hydrogen bonds
Where are the side chains for beta pleated sheets?
They lie alternately above and below the plane of the sheet
What makes a protein structure a tertiary structure?
The complete pattern of folding of the full length of the polypeptide and it’s the 3D structure from the packing of various secondary structure elements (only one polypeptide chain though)
What is a protein with quaternary structure?
There is more than one polypeptide chain, each with primary, secondary and tertiary structure. The spatial arrangement of the chains and the nature of their interaction is called quaternary structure
What is the name of each folded chain making up the quaternary structure?
A subunit
What is Gibbs free energy?
The maximum reversible work that may be performed by a system at constant temperature and pressure
What is the equation for the change of Gibbs free energy involving enthalpy and entropy?
The change in enthalpy minus the temperature multiplied by the change in entropy
What is enthalpy (H) and does an increase or decrease lead to more spontaneity in a process?
Total energy including chemical potential energy and enthalpy decrease = more spontaneity in a process
What is entropy (S) and does an increase or decrease lead to more spontaneity in a process?
Number of ways to arrange the system and entropy increase = more spontaneity in a process
How is temperature and entropy related? (not a formula)
If the reaction occurs at a high temperature, there will be a bigger effect of entropy
Does the change in Gibbs free energy being positive or negative relate to a spontaneous process?
Positive = not spontaneous. Negative = spontaneous.
Out of primary, secondary and tertiary structures, which have the highest and lowest entropy and enthalpy?
Primary has highest of both whilst tertiary has lowest of both
When is folding and unfolding favoured for tertiary structures? (involves temperature and the change in Gibbs free energy)
At low T, change in Gibbs is negative, folding is favoured. At high T, change in Gibbs is positive, unfolded state favoured.
What is the conformational entropy change on folding to a defined state?
The gas constant multiplied by ln P, where P is the estimated probability of the folded state
Is protein folding spontaneous?
Yes
What are the ‘contacts’ that contribute to the enthalpy in a protein folding system?
Formation of disulfide, electrostatic interactions, hydrogen bonding and Van der Waals attraction
What contributes to entropy for protein folding systems?
Water-hydrophobic effect and conformational entropy
What part of amino acids can act as full positive or negative charges in a protein?
Some side chains at certain pHs
What are the charge-dipole interactions between when considering the energy involved in protein folding?
The ionised side chains of amino acids with the dipole of the water molecule
Where do the majority of the amino acids with charged or polar side chains go on globular proteins?
On the exterior surface
In general, are hydrogen bonds stronger than other dipole-dipole interactions or covalent bonding?
Stronger than other dipole-dipole interactions but weaker than covalent bonding
Are hydrogen bonds stronger when they are shorter or longer?
Shorter
Why must dipoles be aligned properly for a hydrogen bond to form?
Hydrogen bonds are directional
What is Van der Waals attraction?
The attraction of intermolecular forces between molecules that is distance-dependent
What are the two types of Van der Waals forces?
weak London dispersion forces (shorter range and more common) and stronger dipole-dipole forces
What are two types of van der Waals attraction where dipoles are involved?
Two molecules with permeant dipoles orienting themselves so attraction results. Also, dipole molecules inducing dipoles in other molecules so that attraction results
How is there van der Waals attraction between non-polar molecules and what is this type called?
The polarisation of one molecule by fluctuations in the charge distribution in a second molecule and vice versa. This is London dispersion forces
What is the effect on water when it is in contact with a hydrophobic surface and why?
It loses entropy because the water molecules becomes highly ordered on the surface, forming the best possible hydrogen bonds (short)
Is it energetically favourable or unfavourable for water to be on a hydrophobic surface?
Unfavourable
Is the hydrophobic effect favourable for enthalpy or entropy?
Enthalpically favourable and entropically unfavourable
Due to the hydrophobic effect, what happens when a flexible protein chain is exposed to water?
The hydrophobic residues hide in the centre and the hydrophilic ones are pushed to the surface
What are disulphide bonds
A covalent bond between two sulphur atoms of two cysteine amino acids to stabilise some protein structures
Where are disulphide bonds most and least stable?
Stable in the extracellular environment (outside the cell) and unstable within a cell
What type of protein do disulphide bonds usually occur in?
Extracellular proteins
What is gene expression?
process by which DNA instructions convert into proteins with two key stages: transcription and translation
What are the 4 types of protein structure?
Primary, secondary, tertiary and quaternary
What is the most common type of protein structure?
Tertiary
What is roughly the volume for one base pair?
1 cubic nanometre
The volume of a container (eg a nucleus) is measured in what amounts usually?
Cubic nanometres
What is the Levinthal paradox?
The correct protein folding by a simple random search is very improbable and would take a long time and yet correctly folded proteins are common and happen relatively quickly
What is the solution to the Levinthal paradox?
Folding is not random and protein sequences contain folding pathway information.
How is the helix shape made in alpha helices?
They have a hydrogen bond every 4th amino acid connected to each other (so there’s 2 amino acids between the connected ones)
What is Gibbs free energy?
maximum reversible work that may be performed by a system at constant temperature and pressure
What is enthalpy (H)?
heat absorbed or released
What is entropy (S)?
measure of disorder in a system
What is the hydrophobic effect when considering protein folding?
causes hydrophobic residues to hide in the centre and hydrophilic residues to be pushed outwards
