From chemistry-request@ccl.net Sat Jun 15 01:21:43 1991 Date: Sat, 15 Jun 91 00:44 EDT From: "Scott Le Grand" Subject: Re: Poly-Ala II To: BLACK@OHSTPHRM.PHARMACY.OHIO-STATE.EDU Status: R >I would still estimate that poly-Ala and poly-Gly will be helical in >CCl4, and that only the latter will unfold in water. But, that brings >up an interesting (ignorant?) question. Can the chlorine atoms of CCl4 >serve as hydrogen bond acceptors? Certainly, there is no net charge on >carbon tet, but significant partial negative charges must be present on >the chlorines. Any thoughts? One of the major problems in the minimization of potential energy functions is accounting for hydration. Although surface area based models seem to reasonably account for this, there are instances where it will clearly be inadequate such as when a water actually incorporates itself into the protein structure, perhaps producing a bump in a helix as a result which could not be modeled without explicitly including solvent. A second problem is chain entropy. If the minimization scheme requires many many iterations, I do not know of a reasonable way to estimate this. This seems to be the most reasonable answer as to why poly-glycine would not stay helical in water. Perhaps Klibanov's results on non-aqueous solvation which predict that a protein is more rigid in non-polar solvents support the idea that poly- glycine would be more likely to remain helical in CCL4 Scott Le Grand From chemistry-request@ccl.net Sat Jun 15 12:27:00 1991 Date: Sat, 15 Jun 91 11:51:13 EDT From: jacque@isadora.albany.edu (Jacque Fetrow) To: chemistry@ccl.net Subject: poly-ala and poly-gly Status: R its time for me to add my $0.02 to this discussion. first, some of the experiments that you guys have been theorizing about have already been done. for structures of poly-glycine, see crick and rich, nature, 1955, vol. 176, p. 780-781 and ramachandran, et al., biochim. biophys. acta, 1966, vol 122, p. 168-170. there are many related references on these model polyala and polygly peptides. second, on whether glycine is a "helix-breaker"... glycine has typically been called a helix breaker because of where it occurs in proteins--in loops and turns at the surface. it may not necessarily be true that glycine is a "helix-breaker," rather that glycine is found more often in loops and turns because it is conformationally more flexible and this backbone flexibility is required in loops and turns, not helices. experimental evidence suggests that glycine is not anymore of a "helix-breaker" than asp, thr, his, and cys, although these residues are at the low end of helix formation in typical host-guest experiments (o'neil and degrado, science, vol 250, p. 646. third, on the question as to whether ccl4 can form hydrogen bonds-- again you can look at experimental data for the answer. in model compounds (n-methylacetamide), thermodynamic parameters for hydrogen bonds have been measured. NMA can form hydrogen bonds with itself in ccl4 and dioxane, but not in water, suggesting that ccl4 and dioxane do not compete as well as water for hydrogen bonding to NMA. (klotz and franzen, j. am. chem. soc., 1962, vol 84, p. 3461. i hope this helps put some experimental data together with your calculations... -jacque fetrow ----------------------------------------------------------------- Jacquelyn Fetrow SUNY-Albany Department of Biological Sciences jacque@isadora.albany.edu jf162@ALBNYVMS.BITNET -----------------------------------------------------------------