400 likes | 447 Vues
Monomers and Polymers. Andy Howard Biology 555, Fall 2018 28 August 2018. Bilayers create a close approximation of a 2-D environment. Kinetics of reactions Rates of diffusion, etc. All very different from what you find in solution, which is an inherently three-dimensional phenomenon.
E N D
Monomers and Polymers Andy HowardBiology 555, Fall 2018 28 August 2018
Bilayers create a close approximation of a 2-D environment • Kinetics of reactions • Rates of diffusion, etc. • All very different from what you find in solution, which is an inherently three-dimensional phenomenon Biology 555: Monomers & Polymers
Interior of protein resembles an organic solvent • Energetically unfavorable to bury charge • Charged amino groups very different properties in interior of protein vs exterior Biology 555: Monomers & Polymers
Configuration vs Conformation • Configuration refers to the arrangement of atoms around non-rotating bonds or chiral centers • Configurations can only be changed by breaking covalent bonds • cis-trans isomers • L-D stereoisomers of proteins • Molecules with the same atomic composition but different configurations may have entirely different chemistry! Biology 555: Monomers & Polymers
Configuration Biology 555: Monomers & Polymers
Conformation Biology 555: Monomers & Polymers
Differences in Conformation involve Rotations around Freely Rotating Bonds • gauche and anti- stereoisomers • eclipsed or staggered • a particular conformation will be more or less energetically favorable • particular conformations will have particular chemical properties Biology 555: Monomers & Polymers
Torsion and Dihedral Angles Biology 555: Monomers & Polymers
Biological Monomers are Generally Chiral Molecules • i.e. lack planes or centers of symmetry • Organic chemistry has conventions to describe absolute configurations • Sugars described with respect to chiral centers • Biopolymers constructed of only one enantiomer of a particular monomer • In amino acids the chiral center is the so-called alpha-carbon • Main-chain sequence of atoms: N-C-C-N-C-C…,where the non-alpha carbon is the carbonyl carbon Biology 555: Monomers & Polymers
Macromolecules can have many different conformations • Typically only one is functional:it’s called the native conformation • Described in terms of the torsion angles (J) around each freely rotatable bond • J ranges from -180- 180 degrees • eclipsed gauche J = 0 • staggered anti J = 180 degrees • dihedral angles are the complement of the torsion angles Biology 555: Monomers & Polymers
Proteins made of amino acids • 20 common ones • All L form except glycine (not chiral) • D-amino acids rarely seen;exceptions have specific functional roles • Some AA’s modified post-translationally • Proteins require cofactors to function • Metal ions, small organic molecules Biology 555: Monomers & Polymers
AA’s can be hydrophobic or hydrophilic • Vary in degree of hydropathy • One can measure from the partition coefficient of an amino acid in an organic solvent(octanol closely mimics interior of protein) • Gives estimate of relative effect on thermodynamic stability of molecule Biology 555: Monomers & Polymers
Shape of side chains important • Aromatic rings in Phe, Trp, Tyr bulky and tend to interact with each other • Planes tend to line up perpendicular to each other in the interior of globular proteins • Benzene molecule line up similarly in solution • Entropy driven i.e. more ways to stack perpendicularly than parallel Biology 555: Monomers & Polymers
Special case: proline • Proline isn’t an amino acid: it’s an imino acid • Hindered rotation around bond between amine N and alpha carbon is important to its properties • Tends to abolish helicity because of that hindered rotation Biology 555: Monomers & Polymers
The simplest amino acids • Glycine • Alanine These are moderately nonpolar methyl Biology 555: Monomers & Polymers
Valine Isoleucine Leucine Branched-chain aliphatic aas Seriously nonpolar isopropyl Biology 555: Monomers & Polymers
Serine Threonine Hydroxylated, polar amino acids hydroxyl Biology 555: Monomers & Polymers
Aspartate Glutamate Amino acids with carboxylate side chains carboxylate methylene Biology 555: Monomers & Polymers
asparagine glutamine Amino Acids with amide side chains amide Note: these are uncharged! Don’t fall into the trap! Biology 555: Monomers & Polymers
Cysteine Methionine Sulfur-containing amino acids sulfhydryl Two differences:(1) extra methylene(2) methylated S Biology 555: Monomers & Polymers
Lysine Arginine Positively charged side chains Guani-dinium Biology 555: Monomers & Polymers
Phenylalanine Tyrosine Aromatic Amino Acids phenyl Biology 555: Monomers & Polymers
Histidine: a special case • Histidine imidazole Biology 555: Monomers & Polymers
Tryptophan: the biggest of all • Tryptophan indole Biology 555: Monomers & Polymers
The Peptide bond • Amino acids condensed by dehydration synthesis • Carboxyl + amino => C-N bond. • i.e. flanked on both sides by -carbons • Formation not spontaneous => need ribosomes • Hard to reverse => need hydrolytic enzymes Biology 555: Monomers & Polymers
The Peptide Bond Biology 555: Monomers & Polymers
Peptide bonds have double bond character • Bond lengths less than normal C-N bond lengths • Resonance structure • Effectively rigid and planar • Barrier of ~13 kJ mol-1 between cis and trans forms • Cis-form highly disfavored because of steric hindrance (except for proline) • There is a small dipole moment across the peptide bond (-ve end carbonyl oxygen) Biology 555: Monomers & Polymers
Double-bond character of peptide Biology 555: Monomers & Polymers
The peptide bond and restrictions on protein conformation • Bond between -carbon and the carbonyl carbon called • Bond between -carbon and the amino group called • Entire peptide bond plane rotates so certain values of and cannot be achieved because of steric hindrance Biology 555: Monomers & Polymers
The result: planarity! • This partial double bond character means the nitrogen is sp2 hybridized • Six atoms must lie in a single plane: • First amino acid’s alpha carbon • Carbonyl carbon • Carbonyl oxygen • Second amino acid’s amide nitrogen • Amide hydrogen • Second amino acid’s alpha carbon Biology 555: Monomers & Polymers
Rotations and flexibility • Planarity implies = 180º,where is the torsion angle about N-C bond • Free rotations are possible about N-C and C-C bonds • Define = torsional rotation about N-C • Define = torsional rotation about C-C • We can characterize main-chain conformations according to , Biology 555: Monomers & Polymers
Ramachandran angles G.N. Ramachandran Biology 555: Monomers & Polymers
Preferred Values of and • Steric hindrance makes some values unlikely • Specific values are characteristic of particular types of secondary structure • Most structures with forbidden values of and turn out to be errors Biology 555: Monomers & Polymers
How far from 180º can w vary? • Remember what we said about the partial double bond character of the C-N main-chain bond • That imposes planarity • In practice it rarely varies by more than a few degrees from 180º. Biology 555: Monomers & Polymers
Secondary Structure • & secondary structures arise from and based steric hindrance • If a sequence consists of AA's with similar allowed and 's & secondary structures may arise independent of details about bonding • Trans conformation • Fully extended AA chain - no intramolecular bonding • Other secondary structures stabilized by hydrogen bonds Biology 555: Monomers & Polymers
Ramachandran plots • Allowed regions of and "phase space" for a particular amino acid shown on Ramachandran plots (different side chains) • Can be defined in terms of hard sphere boundaries or energy cost to enter particular regions Biology 555: Monomers & Polymers
Ramachandran Plot for Poly-L Alanine Contours of vDW interaction energies Dark allowed Cross-hatched possible Blank areas not allowed P=polyproline C=collagen helix 310 & helices left & right helices, parallel, anti-parallel sheets Biology 555: Monomers & Polymers
Ramachandran Angles in Proteins Biology 555: Monomers & Polymers
Ramachandran plot • Cf. figures in text • If you submit a structure to the PDB with Ramachandran angles far from the yellow regions, be prepared to justify them! Biology 555: Monomers & Polymers
Structure of Nucleic Acids • polynucleotide chains highly flexible • range of allowed conformations much greater than for polypeptide chains • because number of torsion angles in back-bone greater • some restrictions, e.g. sugar pucker • The angle around the glycosidic bond is restricted to be between -180º and -90º for the anti comformation and -90º and 190º for the syn conformation Biology 555: Monomers & Polymers