1.

What is a chemical bond

Chemical bond is any rearrangement of electrons in two atoms that generates a force, causing the
atoms to be bound to each other, forming a molecule. It can result from sharing of electrons as in
covalent bond or from transfer of atoms as in ionic bond.
2. Why it is worth to keep this notion in mind
Because the properties and the behavior of macromolecules depend on the properties of their
constituent components and the types of chemical bonds between them.
3. Which types of chemical bonds are known
Chemical bonds can be divided in 2 categories: covalent and non-covalent bonds. Covalent bonds
result from sharing of electrons between two atoms and can be polar or non-polar. Polar covalent
bonds are formed between different elements that attract the shared electrons to a different level
(H and O atoms in water) while non-polar covalent bonds are formed between two atoms of the
same element (C-C bond). Non-covalent bonds are ionic bond and hydrogen bond. Ionic bond is
based on the transfer of electrons from one atom (cation) to another atom (anion). Hydrogen
bond is an attractive interaction between a hydrogen atom from one molecule or a molecular
fragment X-H (where X is more electronegative than H) and an atom or a group of atoms in the
same or a different molecule in which there is evidence of bond formation.
4. The major characteristics of a chemical bond
Major characteristics of a chemical bond are bond distance (distance between nuclei of the two
atoms involved), bond energy (energy required to break the bond) and bond order (number of
bonds between the two atoms).
5. How can we define the bonding energy
Bonding energy is the measure of bond strength. It is a function of internuclear distance between
two atoms. At large distances it is zero, meaning that there is no interaction. By decreasing the
distance the energy increases reaching its maximum (most negative value) at the equilibrium bond
distance. Further decreasing the internuclear distance causes repulsive forces and the energy
decreases (becomes more positive). In general, the stronger the bond between two atoms the
short their internuclear distance.
6. Pairwise interactions: how many types can you describe
a. Covalent bond
b. Charge - charge (Coulomb energy)
c. Charge - dipole
d. Charge - non polar
e. Van der Waals interaction:
i. Dipole - dipole (Keesom energy)
ii. Dipole - non polar (Debye energy)
iii. Two non-polar molecules (London dispersion energy)
f. Hydrogen bond
7. What is a dipolar interaction?
Dipolar interaction is the interaction between two polar molecules (having a partial positive
charge on one end and a partial negative charge on the other end and thus a dipole moment).
There is attraction between opposite partial charges and a repulsion between same partial
charges. Therefore two freely rotating dipoles tend to orient themselves in space so that their
oppositely charged ends are adjacent. Because each end of a dipole possesses only a fraction of an
electron charge, dipole - dipole interactions are much weaker than charge - charge interactions.
8. Why a peptide bond is a dipole?
Peptide bond is a covalent bond between a carboxyl group of one amino acid and an amino group
of the other amino acid. The resonance increases the polarity of the peptide bond causing a partial
 positive charge at the N-terminus and a partial negative charge at the C-terminus. This can make
an important contribution to the behaviour of folded proteins.
9. The hydrophobic effect: a definition
Hydrophobic effect is the tendency of nonpolar substances to aggregate in aqueous solution and
exclude water molecules. Interactions between hydrophobic molecules enable the displaced
water molecules to make hydrogen bonds more freely with each other decreasing the overall free
energy. Substances for which this effect is observed are known as hydrophobes. Hydrophobic
effect is responsible for the separation of the mixture of water and oil, cell membranes and
vesicles formation, protein folding, insertion of membrane proteins into the nonpolar lipid
environment and protein - small molecule associations therefore it is essential to life.
10. Why a lipid bilayer is stable
Lipid bilayer is stable because all of its constituent molecules are in a low energy state.
Hydrophobic effect causes amphipathic phospholipids in an aqueous environment to orient
themselves so that their polar heads form electrostatic interactions with water molecules and
their apolar tails form hydrophobic interactions, creating a bilayer.
11. The hydrogen bond: why is it so important ?
Hydrogen bond is an attractive interaction between a hydrogen atom from one molecule or a
molecular fragment X-H (where X is more electronegative than H) and an atom or a group of
atoms in the same or a different molecule in which there is evidence of bond formation. Its a
week interaction but the combined effect of many week bonds is not trivial. The hydrogen bond is
the major stabilizing force in bio-molecules. It plays a crucial role in many biological processes and
can account for many natural phenomena such as the properties of water, base pairing and the
formation of the secondary structure of proteins.
12. Water molecules: the dominant interactions
The dominant interactions between water molecules are hydrogen bonds. Positively charged
region of one water molecule (one of its H atoms) interacts with a negatively charged region (O
atom) of a second water molecule. Each water molecule can form hydrogen bonds with two other
water molecules producing a network in which bonds are continually broken and formed. This
bond is much weaker than a covalent bond ((G0)=-3/-5 Kcal/mol) and easily broken by random
thermal motions.
13. Permanent dipoles versus transient dipoles
Dipoles are molecules that have a partial positive charge on one end and a partial negative charge
on the other end. Permanent dipoles are permanently polarized molecules resulting from a polar
covalent bond (between atoms that have different electronegativities). Transient dipoles are non-
polar molecules that become polarized because of the random fluctuation of electrons which then
induces polarity in the neighbouring molecule.
14. The role of electrostatic interactions at a molecular level
Electrostatic interactions are of fundamental importance in determining the structure, dynamics,
and function of biomolecules. In particular, they play a key role in protein folding and stability, pH-
induced conformational changes, recognition of substrates by receptors, enzymatic catalysis, etc.
These electrostatic interactions make an especially large contribution to the folded structure of
nucleic acids, because the monomers each carry a full negative charge.
15. Van der Waals interactions: how would you rate them among the non-bonding interactions
Van der Waals interactions are the weakest among the non-bonding interactions ((G0)=-0,5
Kcal/mol).
16. The simplest definition of chemical reaction
 Chemical reaction is a process that leads to the transformation of reagents into products. It can be
described by a chemical equation. Chemical reactions happen at a characteristic reaction rate at a
given temperature and chemical concentration.
17. Which equation describes the dissociation processes
For a generic dissociation process AxByxA+yB the dissociation constant is defined as
Kd=([A]^x[B]^y)/[AxBy]
18. What is the pKa of a substance
pKa is a measure of the acidity of a substance: pKa = -logKa, where Ka is the acid dissociation
constant. For a generic acid HA that dissociates with the equilibrium: HA + H2O A- + H30+, Ka
is defined as Ka = [A-]*[H30+]/[HA], where [] are the concentrations of the species in the
solution. In other words, this constant expresses the strength of an acid. If the Ka is high, the pKa
is low and the acid is strong. If the Ka is low, the pKa is high and the acid is weak. For an acid, it
also can be expressed as: pKa = pH + log([HA]/[A-]), and it means that when we have [HA] equal to
[A-], the pKa of the substance coincides with its pH..
19. What characterizes a molecule
A molecule is a set of two or more atoms held together by chemical bonds. The main features of a
molecule are the type and number of molecules that compose it, the type of chemical bonds
between the atoms and its geometry (how the atoms are placed in space).
20. When a molecule is water soluble
A molecule is water soluble when it is either charged or polar (has partial positive and partial
negative charges). Both charged and polar molecules can form hydrogen bonds with water
molecules. Specifically, the partial positive end of the water dipole (H atom) interacts with the
partial negative end of the molecule and its partial negative end (O atom) interacts with the
partial positive end of the molecule.
21. When a molecule is water insoluble
A molecule is water insoluble when it is apolar (its charge is uniformly distributed). Being apolar
means that it cannot form hydrogen bonds with water dipoles and therefore is not soluble.
Instead, it tends to "escape" water by minimazing its exposure to it (aggreggates with other
hydrophobic molecules).
22. What is affecting the atomic reactivity
The atomic reactivity is influenced by the atomic size and the number of valence electrons
(electrons of the outermost shell of the atom). The larger the atom the more reactive it is because
its electrons are further away from the nucleus and can therefore form bonds more easily. The
smaller the number of valence electrons the atom has to gain/loose in order to obtain a full
outermost shell the more reactive the atom is.

PART III
1. At constant temperature, in spontaneous phenomena the entropy change is increasing or
decreasing
At constant temperature a phenomena is spontaneous when G<0. Considering the equation
G=H-TS we have the following possibilities for a spontaneous phenomena:
o S > 0 and H < 0 (entropy is increasing)
o S > 0 and H > 0, at high temperatures (entropy is increasing)
o S < 0 and H < 0, at low temperatures (entropy is decreasing)
2. Which is the discipline that bridges microscopic and macroscopic descriptions
3. Why thermodynamics is so important in biology
4. The field of application/s of thermodynamics
5. The definition of an equilibrium constant with constraints
 The equilibrium constant of a chemical reaction is the value of the reaction quotient when the
reaction has reached equilibrium. An equilibrium constant value is independent of concentrations
of the reactant and the product in a mixture, but depends on temperature and on ionic strength.
Known equilibrium constant values can be used to determine the composition of a system at
equilibrium.
6. The role of the Gibbs free energy change
Gibbs free energy change can be used for determining the spontaneity of a process. If G defined
by the equation G=H-TS is negative then the process is spontaneous, if it is 0 the process is at
the equilibrium, if it is positive the process is non-spontaneous.
7. What is a standard condition
A standard condition is a condition of a system characterized by the following properties:
a. Temperature equal to 298K (25 C)
b. Pressure equal to 1 atm
c. pH equal to 7.0 as in pure water
d. Concentration for all reactants and products equal to 1 M
8. How are entropy, enthalpy and Gibbs free energy related
Entropy, enthalpy and Gibbs free energy are related through the following equation: G=H-TS.
9. A definition of pH
pH is a value expressing acidity or alkalinity of a solution on a logarithmic scale on which 7 is
neutral, lower values are more acidic and higher values are more alkaline. It is calculated by the
following formula: pH = -log[H+] (where [H+] is the concentration of the H+ ions in the solution).
10. A definition of hydrophobicity
Hydrophobicity is a physical property of a molecule (known as hydrophobe) to not interact with
water. Hydrophobes are non-polar and hence cannot form hydrogen bonds with polar water
molecules.

PART IV
1. What is a model?
A model is a mathematical relation among physical quantities that allows to make predictions on a
specific phenomenon.
2. Which is the difference among variables and parameters in a model?
Variable is an entity whose value changes based on the values of other entities in the model while
a parameter is an entity whose value can also change but once fixed defines a whole class of
models.
3. The basic equations of thermodynamics: why are they so important?
The basic equations of thermodynamics are the following:
U=Q-W, H=U+pV (enthalpy), S=Qrev/T (entropy), G=H-TS.
They are so important because they permit us to relate heat and temperature of a system with its
work and energy.
4. Which is the most important thermodynamic equation in biological systems?
The most important thermodynamic equation in biological systems is the following:
G= -RTlogKeq (where G is the change in Gibbs free energy under normal conditions, R is the
gas constant R=8,314 J/(mol*K), T is the temperature in K and Keq is the equilibrium constant).
5. What is kinetics adding to modelling of a phenomenon?
Kinetics is adding the information about the reaction rate of a phenomenon and about factors that
affect the rate (e.g. temperature, concentrations, nature of reagents, etc.).
6. Which are the most important enzyme kinetic models?
The most important enzyme kinetic models are Michaelis-Menten equation and Hill's equation.
 Michaelis-Menten equation is the following:
v=(Vmax*[S])/(Km+[S]) (where v is the reaction rate, Vmax is the theoretical maximal rate, S is the
concentration of the substrate and Km is the Michaelis constant Km=(k-1+k2)/k1).
Hill equation is the following:
v=(Vmax*[S]n)/(Kmn+[S]n) (where v is the reaction rate, Vmax is the theoretical maximal rate, S is the
concentration of the substrate and Km is the Michaelis constant Km=(k-1+k2)/k1 and n is the Hill
coefficient that describes cooperativity).
7. Can you write the equation of the chemical potential as a function of the concentration?
Chemical potential as a function of the concentration is given by the following formula:
i = i + RTlogCi (where i is the chemical, i is the chemical potential in standard conditions, R is
the gas constant R=8,314 J/(mol*K), T is the temperature in K and C is the concentration of the
chemical).
8. And that of the chemical potential difference?
Chemical potential difference is given by the following formula:
i = RTlog(CiB/CiA) (where i is the chemical, R is the gas constant R=8,314 J/(mol*K), T is the
temperature in K, C is the concentration in the two phases A and B in which the chemical is
present (e.g. the two water phases separated by the cell membrane).
9. What is a kinetic constant?
Kinetic constant quantifies the rate of a kinetic reaction. It depends on the temperature.
10. Which is the relation between the rate constant and the equilibrium constant
The relation between the equilibrium constant and the rate constants of a reversible reaction is
the following:
Keq = kf/kr (where kf is the rate constant of the forward reaction and kr is the rate constant of the
reverse reaction).

PART V
1. A definition of DNA
DNA is heteropolymer of monomers called deoxyribonucleotides that are linked by a
phosphodiester bond. It stores genetic information because its sequence contains instructions for
protein synthesis.
2. Why DNA is storing genetic information
DNA is storing genetic information because the DNA sequence contains instructions for protein
synthesis. It can guarantee an accurate (because of base pairing univocity and the mismatch repair
system) and unlimited replication (because of semi conservation) and can be contained within the
tiny space of the cell (because of supercoiling).
3. How can you read DNA composition
4. Why DNA is a polar molecule
DNA is a polar molecule because phosphate groups in its backbone are negatively charged.
5. Differences among DNA and RNA
The differences between DNA versus RNA are the following:
a. Function: DNA stores and transmits genetic information while RNA transfers the genetic
information from nucleus to ribosomes for protein synthesis.
b. Structure: DNA is typically double stranded and long while RNA is typically single stranded
and shorter.
c. Sugar/bases: DNA contains the sugar deoxyribose while RNA contains the sugar ribose (has
one more -OH group than deoxyribose). DNA has thymine instead of uracil present in the
RNA.
 d. Base pairing: In DNA there is adenine-thymine bond while in RNA there is adenine - uracil
bond.
e. Stability: DNA is stable under alkaline conditions while RNA is not. DNA has smaller grooves
while RNA has larger grooves (easier for an enzyme to attach)
6. DNA supramolecular organization: how to fit about 1 meter of DNA in a volume of 4/3 m3
In its "relaxed" state DNA is a 1,8 meter-long double-stranded helix. It is combined with histones
to make nucleosomes. Each nucleosome consists of 8 histones (2 of each of the four types: H2A,
H2B, H3 and H4) around which DNA is wrapped 1,65 times. A chromatosome consists of a
nucleosome plus the H1 histone. The nucleosomes fold up to produce a 30-nm fiber that forms
loops averaging 300 nm in length. The 300-nm fiber is compressed and folded to produce a 250-
nm wide fiber. Tight coiling of the 250-nm fiber produces the chromatid of a chromosome.
7. Protein synthesis: why a biological process
Protein synthesis is a biological process because it is completely carried out in a biological cell.
8. The major steps of the information flow during protein biosynthesis
The major steps of the information flow during protein biosynthesis are: 1) transcription of DNA
resulting in a complementary RNA; 2) post-transcriptional modifications (e.g. capping, splicing)
resulting in a mature mRNA; 3) mRNA translation via ribosomes in the cytoplasm resulting in the
peptide; 4) post-translational folding and consequent acquisition of functionality.
9. The genetic code: how would you define it
Genetic code is a set of rules by which the information encoded within genetic material (DNA or
mRNA) is translated into proteins. The code binds a triplet of nucleotides (codon) to a specific
amino acid. It is highly similar among all organisms and can be expressed in a simple table with 64
entries.

PART VI
1. Proteomics: the goal
The goal of proteomics is to define the protein content of the cell and to describe how it changes
in response to different physiological states.
2. How can you define a protein?
Protein is a heteropolymer of monomers called amino acids. It is a complex system capable of
auto-organization in the space of a polar solvent.
3. Why a 20 letter code for a protein?
Because there are 20 different amino acids and proteins are heteropolymers of amino acids their
sequence can be defined with a 20 letter code.
4. Amino acids: how many, distinctive features, and major classification
There are 20 different amino acids. Every amino acid is composed of a carboxyl group, an amino
group and a residue with specific physico-chemical characteristics. Amino acids form peptide
bonds with each other. There are essential amino acids (need to be acquired through the diet) and
non-essential amino acids. Based on the residues they can be classified as:
o hydrophobic (escape the interaction with the polar solvent): alanine, valine, leucine,
isoleucine, glycine, proline;
o aromatic (with an aromatic ring): phenilalanin, tyrosin, triptophane;
o polar (stabilised by interaction with polar solvent): histidine, arginine, glutamine, serine,
threonine;
o charged (characterized by local positive or negative charged groups at physiological pH):
lysine, asparagine, aspartic acid, glutammic acid.
5. Can you describe a peptide bond?
 Peptide bond is a covalent bond between a carboxyl group of one amino acid (releases OH-) and
an amino group of another amino acid (releases H+). In this reaction a water molecule is also
formed from the hydroxyl group and the hydrogen atom. Amide bonds are very stable in water at
neutral pH. The resonance increases the polarity of the peptide bond causing a partial positive
charge at the N-terminus and a partial negative charge at the C-terminus. This can make an
important contribution to the behaviour of folded proteins.
6. When do you know the protein structure?
You know the protein structure when you can describe its electron density. The electron density is
used to determine the coordinates of the atoms.
7. How can you state that there is a relation between structure and function? - NOT IN EXAM
8. How would you describe a protein function? - NOT IN EXAM
9. What is a biological process?
A biological process is a process vital for a living organism. Biological processes are made up of
many chemical reactions or other events that are necessary for the persistence or transformation
of life forms. Metabolism and homeostasis are examples.
10. A metabolic pathway?
A metabolic pathway is a chain of chemical reactions occurring in a cell. These reactions are
catalysed by enzymes and the product of one enzyme acts as the substrate for the next. A
metabolic pathway can be either catabolic or anabolic.
11. Do you have a definition for reactome?
12. Why the residue composition is affecting protein structure?
Residue composition is affecting protein structure because depending on the organization of the
various amino acid residues we have different folding of the protein and therefore, different
structure.
13. Genomics, transcriptomics, proteomics, regulomics, metabolomics: why so many omics?
There are many different omics because each one focuses on a different cellular content:
genomics on the genome, transcriptomics on mRNAs, proteomics on proteins, regulomics on
biological regulation and metabolomics on metabolites.
14. Protein backbone vs lateral side chains
Protein backbone is the repeating portion of the polypeptide chain composed of the N-H group,
the alpha-carbon C-H group and the C=O of each amino acid. Lateral side chains protrude from the
backbone and represent the residues of the amino acids. There are 20 different residues.
15. Major hierarchical organisations of protein structure
Primary structure of a protein is the sequence of amino acids that make up the polypeptide chain.
Secondary structure refers to folding patterns of the backbone such as alpha helices and beta
sheets. Tertiary structure is the overall 3-dimensional folding of the polypeptide chain. Quaternary
structure is obtained by assembling multiple polypeptide chains.