Joined: Dec. 2002
An inference to the best explanation here is that the IDers do a dismal job of explaining themselves. When so many intelligent and educated individuals have so many similar "misconceptions" about a position that has been around since the time of Aristotle, it seems to me that the IDers ought to do some introspection and blame themselves.
|I decided to join this group (among others) mostly because I suspect that there are a lot of misconceptions about intelligent design.|
I was not aware that hydrophobic interactions played any more of a significant role in alpha helix and beta sheet formation and elongation(!?), than, say, polar interactions between side chains, or hydrogen bonding between the amino and carbonyl groups of the peptide backbone. Perhaps you have misquoted some source.
|One of the major points in this essay is that Hydrophobic interactions play a large role in protein folding and structure as well as alpha helix and beta sheet elongation/formation [...]|
Yet this is an odd observation, especially after mentioning the importance of hydrophobic interactions in the same breath, since serine is after all a polar amino acid (hydroxy side chain).
|[...] further substantiation of this is shown from the fact that serine and not proline, which is a helix breaker, is formed after C-T transitions.|
OK. But so are all other types of mutations. A major assumption made in your argument is that, of the changing properties in amino acids resulting from C-T transitions, the differences in hydrophobicity dominate over, say, steric effects and other structural characteristics with regards to overall protein structure. Otherwise, it does not seem to me that you can say C-T transitions affect evolutionary pathways through a particular mechanism (i.e. changes in hydrophobicity), especially in a manner that suggests intelligent foresight. However, consider for instance Arg (CG_) -> Cys (UG_) changes. Is the potential of the new Cys in forming new disulfide bonds with other Cys residues necessarily a negligible effect when compared to the changes in hydrophobicity? The problem here is that you have greatly oversimplified the mechanisms underlying the propensities for alpha and beta chain formation. A single residue and its specific properties do not by themselves determine peptide folding.
| So C-T transitions are used to evolve new proteins. |
I do not follow this train of logic. It appears to be a weak argument that comes in the form of ad hoc reasoning. If A then B, and B is true... but that says nothing logically about the premise A (i.e. that some state was "front-loaded"). Furthermore, if we posit some initial state C0, from which life evolves, who is to say that there does not exist an earlier state B0 which gives rise to C0? At the very least, the argument presented thus far does not rule that possibility out. Going in the other direction, let us suppose that C0 gives rise to C1, which in turn gives rise to C2, etc. ... all the way up to Cn, which we currently observe. While we are positing the intentions of the designer, wouldn't it make more sense for the designer to put desirable qualities of the later states directly into C0? Why bank on stochastic processes that perhaps might not evolve an intended later stage? It may very well be that C-T transitions coincide with certain evolutionary mutations. So what? This observation alone says nothing about ID, it seems, without doing some additional guesswork about the Designer's thinking. But, ID has yet to offer us any evidence what the Designer cannot do or constraints on his designs.
|"This hypothesis also makes a prediction that can be tested. For example, if the multicellular state was front-loaded with life's design, we would expect to find conserved, multicellular-specific proteins have crucial FLIYWVMCS residues that can [be] explained by C-T transitions relative to their ancestral state"|
I understand that Mike Gene is the IDer du jour, and so typically many IDers would naturally begin to parrot the latest ID scientist. But in this case, I don't even think you took the time to read his essay carefully.
edited to add citations for some articles (that are more recent than 1979) on helix-forming propensities from a quick Pubmed search:
|Proteins 1999 Mar 1;34(4):497-507|
Hydrogen bonds between short polar side chains and peptide backbone: prevalence in proteins and effects on helix-forming propensities.
Vijayakumar M, Qian H, Zhou HX.
Department of Physics and Atmospheric Science, Drexel University, Philadelphia, Pennsylvania 19104, USA.
A survey of 322 proteins showed that the short polar (SP) side chains of four residues, Thr, Ser, Asp, and Asn, have a very strong tendency to form hydrogen bonds with neighboring backbone amides. Specifically, 32% of Thr, 29% of Ser, 26% of Asp, and 19% of Asn engage in such hydrogen bonds. When an SP residue caps the N terminal of a helix, the contribution to helix stability by a hydrogen bond with the amide of the N3 or N2 residue is well established. When an SP residue is in the middle of a helix, the side chain is unlikely to form hydrogen bonds with neighboring backbone amides for steric and geometric reasons. In essence the SP side chain competes with the backbone carbonyl for the same hydrogen-bonding partner (i.e., the backbone amide) and thus SP residues tend to break backbone carbonyl-amide hydrogen bonds. The proposition that this is the origin for the low propensities of SP residues in the middle of alpha helices (relative to those of nonpolar residues) was tested. The combined effects of restricting side-chain rotamer conformations (documented by Creamer and Rose, Proc Acad Sci USA, 1992;89:5937-5941; Proteins, 1994;19:85-97) and excluding side- chain to backbone hydrogen bonds by the helix were quantitatively analyzed. These were found to correlate strongly with four experimentally determined scales of helix-forming propensities. The correlation coefficients ranged from 0.72 to 0.87, which are comparable to those found for nonpolar residues (for which only the loss of side-chain conformational entropy needs to be considered).
|Proteins: Structure, Function, and Genetics|
Volume 39, Issue 2, 2000. Pages: 132-141
The relative order of helical propensity of amino acids changes with solvent environment
Chartchai Krittanai, W. Curtis Johnson Jr
A model peptide of sequence Ac-Y-VAXAK-VAXAK-VAXAK-NH2, where X is substituted with one of nineteen amino acids (P excluded), was synthesized and titrated with methanol to study helical propensity as a function of solvent environment. The CD spectra of these peptides are largely random coil in 2 mM sodium phosphate buffer (pH 5.5) and show a conformational change to -helix with increasing methanol content. Singular value decomposition was used to correct the CD spectra for the absorbing side chains of W, Y, F, C, and M, and this correction can be substantial. With correction both W and F become good helix formers. The free energy for helix propagation was calculated using the Lifson-Roig statistical model for each of the nineteen amino acids at each point in their titration. The results show that the rank order of helical propensity for the nineteen amino acids changes with solvent environment. This result will be particularly important if proteins undergo hydrophobic collapse before secondary structures are formed, because amino acids can then see different solvent environments as the secondary structures are formed. Related amino acids are found to have interesting correlations in the shape of their titration curves. This finding provides one explanation for the limiting 70% accuracy in predicting secondary structure from sequence, since the helical propensities used are calculated for an average solvent environment.
Our absolute values of G0 for the propagation of a helix by a particular amino acid were calculated from the measurements by using the Lifson-Roig statistical model, which is two-state in residues. They can be compared with the results of Rohl et al. and Yang et al. , which were calculated in the same way. The buffer systems were different among the three laboratories, as were the temperatures for the experimental measurements. Rohl et al. made their measurements at 0°C, Yang et al. at 4°C, while we made our measurements at 25°C. In aqueous solution, Rohl et al. find only one residue, A, that favors -helix formation (G0 less than -0.05). Yang et al. find two, A and E. We find seven: W, L, A, F, E, M, and D, with W and L better than A. Part of this difference is undoubtedly due to our correction for the CD of the aromatic side chains that reveals F and W as helix formers. It is possible that ion-ion interactions make D and E better helix formers for our host peptide but our analysis of the titration profiles above argues against this explanation. Rohl et al. find eight amino acids that are helix formers in 40% TFE: A, E, I, K, L, M, Q, and R, although they did not include the aromatic amino acids in these measurements. In 88% methanol we find only four amino acids that are not helix formers: C, D, G, and Y. Clearly solvent environment is important in determining the helical propensity of the amino acids. In 40% TFE Rohl et al. still find A to be the best helix former, but in 88% methanol we find ten amino acids that exceed A in their helix forming ability: W, F, I, Q. R, E, L, K, M and V. Rohl et al. find five amino acids that are significant helix breakers (G0 greater than 0.20) in 40% TFE: S, H, C, D, and G. We find only one in 88% methanol, G.
| J Mol Biol 1998 Apr 24;278(1):279-89|
Position dependence of non-polar amino acid intrinsic helical propensities.
Petukhov M, Munoz V, Yumoto N, Yoshikawa S, Serrano L.
European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, Heidelberg, D-69012, Germany.
Until now and based on the success of the helix/coil transition theory it has been assumed that the alpha-helical propensities of the amino acids are position independent. This has been critical to derive the set of theoretical parameters for the 20 natural amino acids. Here, we have analyzed the behavior of several non-polar residues, Val, Ile, Leu, Met and Gly at the N-cap, at each position of the first helical turn and at a central helical position of a 16-residue peptide model system that starts with eight consecutive alanine residues. We have interpreted the results from these experiments with the model of the helix/coil transition (AGADIR), that indicates that the intrinsic helical propensity is position dependent. Gly, Val and Ile are more favorable at the first turn than in the middle of the alpha-helix, while for Leu and Met we observe the opposite behavior. The differences between the observed helical propensities are as large as 1.0 kcal/mol in some cases. Molecular modeling calculations using the ECEPP/2 force-field equipped with a hydration potential show that this effect can be explained by the combination of three factors: (a) the side-chains in the first helix turn are more solvent-exposed; (b) they have fewer intramolecular van der Waals' contacts; and ( c) they posses higher configurational entropy than that in the central position of an alpha-helix. The position-dependent results of the calculations are in reasonable agreement with the experimental estimates and with the intrinsic propensities of the amino acids derived from the statistical analysis of the protein structure database.
|Fold Des 1998;3(2):119-26|
Tolerance of a protein helix to multiple alanine and valine substitutions.
Gregoret LM, Sauer RT.
BACKGROUND: Protein stability is influenced by the intrinsic secondary structure propensities of the amino acids and by tertiary interactions, but which of these factors dominates is not known in most cases. We have used combinatorial mutagenesis to examine the effects of substituting a good helix-forming residue (alanine) and a poor helix-forming residue (valine) at many positions in an alpha helix of a native protein. This has allowed us to average over many molecular environments and assess to what extent the results reflect intrinsic helical propensities or are masked by tertiary effects. RESULTS: Alanine or valine residues were combinatorially substituted at 12 positions in alpha-helix lambda repressor. Functional proteins were selected and sequenced to determine the degree to which each residue type was tolerated. On average, valine substitutions were accommodated slightly less well than alanine substitutions. On a positional basis, however, valine was tolerated as well as alanine at the majority of sites. In fact, alanine was preferred over valine statistically significantly only at four sites. Studies of mutant protein and peptide stabilities suggest that tertiary interactions mask the intrinsic secondary structure propensity differences at most of the remaining residue positions in this alpha helix. CONCLUSIONS: At the majority of positions in alpha-helix lambda repressor, tertiary interactions with other parts of the protein can be viewed as an environmental "buffer" that help to diminish the helix destabilizing effects of valine mutations and allow these mutations to be tolerated at frequencies similar to alanine mutations.
And here is one on beta sheet propensities:
I will add more recent research if the discussion deems it necessary.
|Proc Natl Acad Sci U S A 1999 Aug 3;96(16):9074-6|
Intrinsic beta-sheet propensities result from van der Waals interactions between side chains and the local backbone.
Street AG, Mayo SL.
Division of Physics, Mathematics, and Astronomy, California Institute of Technology, MC 147-75, Pasadena, CA 91125, USA.
The intrinsic secondary structure-forming propensities of the naturally occurring amino acids have been measured both experimentally in host-guest studies and statistically by examination of the protein structure databank. There has been significant progress in understanding the origins of intrinsic alpha-helical propensities, but a unifying theme for understanding intrinsic beta-sheet propensities has remained elusive. To this end, we modeled dipeptides by using a van der Waals energy function and derived Ramachandran plots for each of the amino acids. These data were used to determine the entropy and Helmholtz free energy of placing each amino acid in the beta-sheet region of phi-psi space. We quantitatively establish that the dominant cause of intrinsic beta-sheet propensity is the avoidance of steric clashes between an amino acid side chain and its local backbone. Standard implementations of coulombic and solvation effects are seen to be less important.