Are there any models for protein folding other than the
(1) side-chain-based (interactions of side-chains dominate the folding process), and
(2) backbone-based (backbone hydrogen bonds dominate the folding process)?
Which one is best in your opinion?
There are two main models for protein folding mechanisms, which are discussed in this review: Article Take home lessons from studies of related proteins
Firstly, there is the diffusion collision mechanism, where secondary structure forms before tertiary structure.
Secondly, there is the nucleation condensation mechanism, where secondary and tertiary structure form concomitantly (i.e. distant regions of the protein can come together at the transition state).
Proteins can also display a mixture of these mechanisms.
More specifically to your question, the fold of a protein is encoded within its amino acid sequence. Therefore, as the backbone is the same regardless of the amino acid (except proline), the side chain is the important determinant in folding. This is both through specific interactions (e.g. hydrophobic) and because specific residues promote different backbone angles (Article Insights into the residual structure in unfolded proteins fr...
).There is very little free energy contribution from backbone hydrogen bonds, as they can be formed with water in the unfolded state, or by neighbouring residues in the folded state (so the number of H-bonds doesn't really change). Satisfying the H-bonds can, however, provide some directionality to folding, without providing stability.
i think that the evaluation of both method is in my opinion mandatory. As you said,
(1) side-chain-based (interactions of side-chains dominate the folding process), and
(2) backbone-based (backbone hydrogen bonds dominate the folding process)
mean that both side chain and backbone have a role in the folding process and stability of protein. In fact, important is the evaluation of all the forces contributing in that process (hydrogen, ionic, vdw ect). Sure the hydrogen bond are strong linkers and have an important role to mantain the protein in the folded state in particular the backbone chain. I think that a good evaluation to estimate the folding is to take into account both contributions. but . . . this is only my opinion i believe that a search to pubmed elucidate well yout doubts.
andrea
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