PROTEIN SCIENCE AM_470145
With additional written (scanned) notes and practice exam with answers
included.
,Inhoud
HC 1_ The basis ....................................................................................................................................... 2
HC 2_ Protein structure ......................................................................................................................... 23
Guest lecture 1_Protein Dynamics ........................................................................................................ 25
HC 3_Protein Function .......................................................................................................................... 35
HC 4_Protein Function Control ............................................................................................................. 43
HC 5_Protein Over-Production .............................................................................................................. 53
HC 6_Protein Interaction ....................................................................................................................... 65
HC 7_Selected methods ........................................................................................................................ 72
HC 8_Protein Engineering ..................................................................................................................... 93
HC 9_Antibiotics and antibiotic resistance............................................................................................ 95
HC 10_New antibiotics ........................................................................................................................ 106
Guest lecture 2_Hydophobicity........................................................................................................... 111
Guest lecture 3_ Molecular Dynamics (MD) simulations of Cytochrome P450 enzymes. .................. 115
Guest lecture 4_Protein-protein interactions (PPIs) ........................................................................... 122
Practice exam 2019-2020 with answers.............................................................................................. 125
,HC 1_ The basis
Atoms contain a nucleus and a cloud of electrons, orbiting around that nucleus. Atoms differ by the
number of positively charged protons within the nucleus and an equal number of negatively charged
electrons.
Electrons do actually not occupy circular orbits as shown here for the sake of simplicity. Instead, they
are distributed into energy levels or shells, and within shells again into orbitals. Orbitals have
complicated shapes that are described by quantum mechanical wave formulas.
Within molecules, atoms are connected by covalent bonds. A single
covalent bond is created by sharing of one pair of electrons. By
sharing electrons, atoms strive to get their outermost orbitals filled.
Electrons are arranged in shells. More stable elements have 8
elements in the outer shell, which are called Noble/inert gasses.
Chemical behavior depends on this characteristic.
Ethene consist of 2C and 4H. In double bonds, four instead of two electrons are
shared. This has consequences for the physical properties of the molecule, e. g. free
rotation is impossible around double. In double bonds there is no 3D orientation,
this is called Trigonal plainer. When there is only a single bound, the molecule could
rotate around that point. The geometric arrangement of Ethene would be a
tetrahedron.
The specific three dimensional arrangement of atoms in
molecules is referred to as molecular geometry. We also
define molecular geometry as the positions of the atomic
nuclei in a molecule.
There are various instrumental techniques such as X-Ray
crystallography and other experimental techniques which can
be used to tell us where the atoms are located in a molecule.
Using advanced techniques, very complicated structures for
proteins, enzymes, DNA, and RNA have been determined.
Molecular geometry is associated with the chemistry of
vision, smell and odors, taste, drug reactions and enzyme
controlled reactions to name a few.
Molecular geometry is associated with the specific
orientation of bonding atoms. A careful analysis of electron
distributions in orbitals will usually result in correct molecular
geometry determinations. In addition, the simple writing of
Lewis diagrams can also provide important clues for the
determination of molecular geometry.
Valence Shell Electron Pair Repulsion (VSEPR) theory: Electron
pairs around a central atom arrange themselves so that they
can be as far apart as possible from each other.
The valence shell is the outermost electron-occupied shell of
an atom that holds the electrons involved in bonding. In a covalent bond, a pair of electrons is shared
between two atoms. In a polyatomic molecule, several atoms are bonded to a central atom using two
, or more electron pairs. The repulsion between negatively charged electron pairs in bonds or as lone
pairs causes them to spread apart as much as possible.
The idea of "electron pair repulsion can be demonstrated by tying several inflated balloons together
at their necks. Each balloon represents an electron pair. The balloons will try to minimize the crowding
and will spread as far apart as possible.
Carbon constitutes the most abundant element in biology (60% of C: atomic number: 6
our body's dry weight). Carbon has 4 electrons in its outer shell, so atomic mass: 12
it has to loose or acquire 4 electrons for outer shell saturation. The electrons in outer shell: 4
respective bonds show tetrahedral orientation. Color: black or grey
E.g. amino acids in proteins are exclusively found in L-configuration. There are no D- amino acids in
proteins (only in the cell wall in bacteria). Carbon has a unique role in the cell because of its ability to
form strong covalent bonds with other carbon atoms. Parafines --> doesn’t react well, only if you burn
them.
If a carbon atom has bound 4 different substituents, asymmetry dictates the existence of two stereo
isomers, an L and an D form. The D- and L- system is named after the Latin dexter and laevus, which
translates to left and right. The assignment of D and L is
used to distinguish between two molecules that relate to
each other with respect to reflection; with one molecule
being a mirror image of the other. These types of
molecules are referred to as chiral for this reason, and the
two pairs are called enantiomers.
D and L isomers are important in pharmacology, as chiral forms of molecules (those of only the L or D
isomer for that molecule) have different physiological effects. For this reason, the isomers can now be
selectively produced. This allows the delivery of medicines containing chiral molecules in a more
targeted, efficacious, and safer way.
Stereoisomers were subsequently referred to as molecules that (1) differ in the organization of their
atoms in space, (2) retain the same constitution, and (3) are related to one another by a plane of
symmetry (are mirror images of one another).
As stereoisomers are present in a pair, they may also be called enantiomers; a term derived from
(enántios), meaning 'opposite', and μέρος (méros), meaning 'part'. Furthermore, the ability of these
molecules to rotate plane-polarized light by an identical magnitude of opposing directions is referred
to as optical activity. The point in the molecule that serves as the anchor for the arrangements of other
groups of atoms in space, such that interchanging the positions of any two groups, is called a
stereocenter.
All amino acids except for glycine are stereoisomers (mirror images of their structure). These are
labeled L-amino acids and D-amino acids to distinguish. Most of the amino acids that are manufactured
today are L-amino acids.
Nitrogen represents the second to most abundant element in N: atomic number: 7
biological dry body mass (11%). With 5 electrons in its outer shell. atomic mass: 14
Nitrogen mostly accepts three electrons to form 3 bonds. electrons in outer shell: 5
Tetrahedron. Because there is an electron pair. Many C-N Color: blue
compounds are building blocks also called functional groups or just
functions. They constitute recurring themes in biochemistry. Shown here is the amine (or amino group,
which can form amide bonds with acidic groups.
