Unformatted text preview:

12phipsi-180 0180-18001803Helices are self stabilizing, after forming the first turn, it becomes much morefavorable to add new residues to the helix. The existing helix generates a helixdipole and this dipole orients additional peptide units to form prefect hydrogenbonds.-Alpha helices are great feats of molecular packing. The interior of the helix istightly packed – Van der Waals interactions galore.-All hydrogen bonds are sequestered from the outside of the helix by the side-chains. So side-chains define overall molecular properties of the helix.-Hydrogen bonds generate and are stabilized by a dipole.-Helix forms its own template for addition of new units.4Energetic consequencesof i+4 hydrogen bondingpattern and helical geometry1) No H-bonds until 4 aain helix2) Repulsion of dipoles ofneighboring peptideunitsThe I+ 4 hydrogen bonding pattern has important consequences for the processof helixFormation in gas phase and protein interior (why not so important in water?).We have to expend conformational entropy for four residues before we get tohave thebenefit of getting back one perfect hydrogen bond. However after that, we getone hydrogenBond for every single additional amino acid. E.g. for 4 aa we have one hydrogenbond for every 4 aa for 8 aa we have one hydrogen bond for every 2. For fortyaa we have approximately one h-bond per aa.56Free energies of helix formation True value ~ -0.3 kcal/mol perresidue for helix propagationHere are the results of some molecular dynamics simulation of helix formation.What we can see is that initiation of the helix is energetically unfavorable andthat the addition of more amino acids to this helix become energeticallyfavorable only after 6-7 amino acids. We can also see the effect of thecompetition between hydrogen bond formation between water and peptides andbetween two peptide units. I the absence of water (I.e. in vacuum) adding newhydrogen bonds contributes about 4 kcal/mol while this energy drops to about0.3 kcal/mol per additional residue in the presence of water.7Beta-branched amino acids such as Val, Ile, Tyr etc. do not like to adopt alphahelical conformations.This effect is partially the result of a loss of conformational entropy experiencedby such side-chainsIn the context of an alpha helix. Use your model of an alpha helix to see whichpf the three staggered conformationsaround the C-alpha-to-C-beta bond a side chain can adopt without causing badsteric clashes.There are only two conformations. If the amino acid is not beta branched, thismeans the multiplicityOf possible conforamtions around that bond is 2 (W=2) if the aa is beta-branched, there is only onePossible conformation (W=1).8Packing helices together: Knobs in HolesIn an aqueous environment, isolated protein helices tend to not be very stablewhen they exist in isolation. To stabilize the helix conformation and to form astable structure, helices need to associate with one another.Here is one of those ways, referred to as knobs in holes packing. This type ofpacking only works is the interacting helices twist around one another. Leu andVal residues are the perfect size to fit into the “ hole” found between fourneighboring amino acids. The most famous class of proteins that uses thispacking mechanism is the Leucine zipper fold.9Leucine zippers often use a combination of “ knob-in-hole” packing with salt-bridges to stabilize the helix-helixInterface. These interaction are sufficiently strong, to not only stabilize theinterface, but also to stabilize the inherentlyunstable helices.10111213Here is an example of a protein in which the packin principle of grooves inridges is taken too the extreme, whereOne simple packing principle is repeated over and over


View Full Document

Brandeis BCHM 104A - Alpha Helix 2007

Download Alpha Helix 2007
Our administrator received your request to download this document. We will send you the file to your email shortly.
Loading Unlocking...
Login

Join to view Alpha Helix 2007 and access 3M+ class-specific study document.

or
We will never post anything without your permission.
Don't have an account?
Sign Up

Join to view Alpha Helix 2007 2 2 and access 3M+ class-specific study document.

or

By creating an account you agree to our Privacy Policy and Terms Of Use

Already a member?