Computational Structural Biology Exam Flashcards
GFP
- green fluorescent protein
- keeps the chromophore planar and facilitates an excited-state proton transfer for the fluorescent coloring
2 types of atomistic interactions
covalent (the framework of biomolecules)
non-covalent (dynamic glue)
covalent
- the framework of biomolecules
- forms when. atoms share pairs of electrons that hold molecules together
ex/ peptide, phosphodiester, glycosidic bonds
peptide bonds
covalently link amino acids into polypeptide chains
phosphodiester bonds
form the sugar-phosphate backbone of DNA and RNA
covalent
glycosidic bonds
join monosaccharides to form complex sugars
covalent
characteristics of covalent bonds
- strength/stability for complex structures
- directionality: covalent bonds limit the specific angles and orientations leading to the 3D shapes of biomolecules
– single bonds allow rotation
– double/triple bonds restrict rotation
directionality of covalent bonds
covalent bonds limit the specific angles and orientations leading to the 3D shapes of biomolecules
– Single bonds: allow rotation, contributing to molecular flexibility
– Double/Triples bonds: restrict rotation, affecting the rigidity and function of molecules
non-covalent bonds
- the dynamic glue
- weaker than the covalent bonds and involve electrostatics (charge dipoles, van der waals)
- drive most of biology
— molecular recognition
— macromolecular structure
types of non-covalent electrostatic interactions
- charge-charge
- charge-dipole
- dipole-dipole
- charge-induced dipole
- dipole-induced dipole
- dispersion (van der Waals)
molecular recognition
Enzyme-substrate binding
Antigen-Antibody interactions
macromolecular structure
Membrane formation
Protein-protein interactions
Base pairing in DNA and RNA
Protein folding
structural biology
- determines the 3D shapes of biological macromolecules and how these shapes relate to functions
why study structural biology?
- Proteins and nucleic acids adopt specific shapes crucial for their biological roles
- Primary Goal: to understand how molecular machines in cells work by deciphering their atomic arrangements
primary structure of a protein
- The linear sequence of amino acids, held together by covalent peptide bonds
- dictates how the protein will fold into higher-order structures
- does not reveal protein’s functional form/activity
- its folding process may depend on cellular factors/chaperones
secondary structure of a protein
- local conformations of the polypeptide chain, stabilized primarily by hydrogen bonds
- structural motif are critical for certain functions
— pleated sheet, alpha helix, 310 helices - undergo local fluctuations – alpha helices can unwind, and beta-sheets can twist – adding to functional flexibility
tertiary structure of a protein
- complete 3D shape of a single polypeptide chain
- reveal active sites or binding pockets were catalysis or molecular interactions occur
- predicting how a sequence folds into its tertiary structure is complex even with knowledge of 2ndary structures
particle behaviors
- determined by quantum numbers (principle, orbital, magnetic)
— based on electrons specific energy levels and characteristics - electrons mix into molecular orbitals based on their specific energy level
*** molecular orbitals are what determine behavior as particles interact with orbitals
*** changing positions changes orbitals
RESULTS in e- density distribution unique to that structure
what causes different e- density distributions?
particles interacting with molecular orbitals and energy levels differently based on positions of e- within structure
3 types of experimental techniques based on probes interacting with molecule’s e- density
- x-ray crystallography
- NMR spectroscopy
- cryo-electron microscopy
x-ray crystallography
- uses how a crystal of molecules diffracts X-rays
Basic Principle: photons scatter when they interact with atoms
Probe: photon (carrier of electromagnetic radiation)
The scattered X-rays form a diffraction pattern unique to the crystal (elastic scattering by e-)
elastic scattering for x-ray crystallography
- Incident photon induces an oscillating dipole by distorting the electron density (Rayleigh)
- An oscillating dipole acts as an electromagnetic source and re-emits photons at the same wavelength in all directions
constructive interference
- needed to amplify the signals of the e- for the detectors of the diffraction pattern
- wavelengths are similar and in phase –> constructively interfere
- waves are out of phase –> destructively interfere
diffraction pattern
- spots on the detector represent the reflections of the scattered X-rays
– Intensity of the spots reflects the electron density in the crystal
– Position and angle of the spots corresponds to the geometry
*** does NOT directly show the atomic positions but provides the data needed to infer e- density