Lecutre 8 Flashcards
Why do we need structural bioinformatics or databases when we already have sequences?
Related proteins structure is much better preserved than sequence.
Structural motifs may predict similar biological function.
Getting insight into protein folding: recovering the limited (?) number of protein folds.
How many amino acids do we have? and what are the diffrent groups of an amino acid
20 naturally occuring amino acids
2 different groups:
Amino group NH2
Carboxyl group COOH
What are the different categories of amino acids based on their side chains?
Size: small, large
Affinity of the water: hydrophobic and hydrophilic
Hydrophobic: aliphatic and aromatic
Hydrophilic: polar and charged
How does the peptide formation occurs?
Peptide formation occurs by two amno acids joining at the OH and H and releasing water.
What is a polypeptide?
Polypeptide: a linear polymer of >50 aa residues
A polypeptide, or a protein, has a well-defined 3D arrangement.
What is a peptide?
Peptide: a polymer with <50 residues without a well-defined 3D structure.
Explain the different parts of the polypeptide: N-terminus and C-terminus
N-terminus: the amino group of the beginning residue of a peptide/polypeptide.
C-terminus: the carboxyl group of the end residue of a peptide/polypeptide.
The sequence of aa residues (1° structure) determines its ultimate structure and function
Explain the dihedral angles
Phi (ϕ): the dihedral angle along the N-Cα bond.
Psi (ψ): the dihedral angle along the Cα-C bond.
Various combination of ϕ and ψ angles allow the proteins to fold in many different ways.
What are the different levels of protein structure?
4 levels:
Primary (1°) structure
Secondary (2°) structure
Tertiary (3°) structure
Quaternary (4°) structure
Explain each level of the protein structure
Primary (1°) structure: Linear aa sequence of a protein
Secondary (2°) structure:Local conformation of a peptide chain: highly regular and repeated arrangement of aa residues stabilized by H-bonds between C=O group and the N-H group of different residues.
Tertiary (3°) structure:Complete 3D assembly of all amino acids of a single polypeptide chain
Quaternary (4°) structure: Association of several polypeptide chains into a protein complex, maintained by non-covalent interactions
What maintains 2 to 4 structures?
Noncovalent forces
What are the different noncovalent forces that main the 2 to 4 structures?
2° to 4° structures are maintained by noncovalent forces:
- Electrostatic interactions
- van der Waals forces
- H-bonding
Explain electrostatic interaction
Electrostatic interactions:excess (–) charges in one region are neutralized by (+) charges in another region
Explain van der waals forces
van der Waals forces:instantaneous interactions b/t atoms when they become transient dipoles
Explain H-bonding
H-bonding:A special type of electrostatic interactions similar to dipole-dipole interaction involving H from 1 residue and O from another.
H-bonding patterns are a dominant factor in determining different types of protein 2° structures.
Explain disulfide bridges
Disulfide bridges:Covalent bonds between the sulfur atoms of the cysteine residue
Explain the different parts of secondary structures
Chief elements:
- α-helices
- β-sheets
α-Helices:
- Corkscrew conformation
- Nearly all right-handed
- Ala, Gln, Leu and Met (NOT Pro, Gly and Tyr)
β-Sheets:
- Fully extended configuration
- Can run in the same direction: parallel sheet
- Run in reverse orientation: anti-parallel sheet
Coiled coil and loops: Irregular local structures
- Coiled coil: bundle of 2+ α-helices wrapping around each other.
- Loop: sharp turns or hair-pin like structures
What are the classifications of tertiary structures?
Various forms but generally classified into:
Globular proteins
Membrane proteins
Exaplain each of the classification of the tertiary structure
Globular proteins:
- exists in solvents through hydrophilic interactions with solvent molecules
- overall compact structure of spherical shape with polar or hydrophilic residues
Membrane proteins:
- exists in membrane lipids and is stabilized through hydrophobic interactions with the lipid molecules.
- the exterior of the protein - very hydrophobic to be stable
What are the two popular experimental techniques that determine the protein 3D structure?
2 popular experimental techniques:
X-ray Crystallography
NMR (Nuclear Magnetic Resonance) Spectroscopy
Explain X-ray crystallography
- Proteins are grown into large crystals so their positions are fixed in a repeated, ordered fashion.
- The protein crystals are then illuminated with an intense x-ray beam.
- The x-rays are deflected by the electron clouds surrounding the atoms in the crystal producing a regular pattern of diffraction.
What are the limitations of the X-ray crystallography?
LIMITATION: whether suitable crystals of proteins of interest can be obtained.
Explain nuclear magnetic resonance spectroscopy
- Detects spinning patterns of atomic nuclei in a magnetic field.
- Protein samples are labeled with radioisotopes such as 13C and 15N
- A radiofrequency radiation is used to induce transitions b/t nuclear spin states in a magnetic field.
- Interactions between spinning isotope pairs produce radio signal peaks that correlate with the distances between them.
What are the limitations of nuclear magnetic resonance spectroscopy
LIMITATION:
(1) protein size limit: must be <200 residues
(2) heavy instrumentation requirement.
What are some exaples of molecular structure visualization forms?
Examples of molecular structure visualizarion forms.
A) Wireframes.
B) Balls and Sticks.
C) Space-filling spheres.
D) Ribbons.
What are some examples of molecular graphic generators
Examples of molecular graphic generated by
A) Rasmol,
B) Molscript,
C) Ribbons, and
D) Grasp
