ValineValine is hydrophobic. Well, this is a true clear fact. But how hydrophobic could it get? Let’s try to understand. When an amino acid is in a peptide sequence, the backbone would tend to folds into a particular conformation, and very importantly, the backbone is polar. How polar? Very polar, too damn polar, even too much. But it would fold into a conformation, and at the exterior there will be amino acid side chains. Remember, that the backbone is still very polar, and it would prefer to have contacts with surrounding water. The side chain can either allow or hinder these contacts. Because valine has a β-branched structure, it covers the backbone like an umbrella, and precludes contacts of the backbone to water. This is why a hydrophobic structure can be featured by valine even better than by leucine, despite the fact that valine is one carbon atom shorter. There is another important outcome of the β-branched structure. Because the side-chain prevents solvation of the backbone, the backbone would like to change its conformation to regain contacts with the solvent. Thus, when valine is in the context of an ?-helix (compact structure, 1.5 Å per an amino acid residue), it can promote its isomerization into a β-strand (extended structure, 3 Å per an amino acid residue), and these can further associate into ?-sheets, and subsequently into amyloid fibrils. This is why valine is often regarded as ?-sheet promoting residue. However, one should understand the reason, why this conformation is promoted by valine, because the statement shouldn’t be generalized too much. The reason is clear differences in the backbone solvation. However, when isomerization occurs between β-strand and PPII helix, both featuring 3 Å per one amino acid residue, the solvation argument becomes more complicated, and in one context valine may preferentially form a PPII helix,* and oppose this conformation in another. The conformational properties of valine are very important, and these play role in peptide design. For instance, by placing valines into a few or even one position in an β-helix, one can promote its isomerization into β-sheets, and subsequently build a model of amyloid formation. * For example in GGXGG model sequences as reported by Shi, Z. et al. Polyproline II propensities from GGXGG peptides reveal an anticorrelation with β-sheet scales. Proc. Natl. Acad. Sci. USA, 102, 2005, 17964-17968, doi: 10.1073/pnas.0507124102 Interesting readings:
- Grling, U. I. M., et al. Concluding the Amyloid Formation Pathway of a Coiled-Coil-Based Peptide from the Size of the Critical Nucleus. ChemPhysChem, 16, 2015, 108-114, doi: 10.1002/cphc.201402400 A kinetic model for amyloid formation built through exchange of a few key positions in an β-helix into valine. - Parent, A. et al. The B12-Radical SAM Enzyme PoyC Catalyzes Valine Cß-Methylation during Polytheonamide Biosynthesis. J. Am. Chem. Soc., 138, 2016, 15515-15518, doi: 10.1021/jacs.6b06697 The paper discusses details of post-translational methylation of valine residues forming tert-leucine in polytheonamide. - Lanza, G. and Chiacchio, M. A. Quantum Mechanics Study on Hydrophilic and Hydrophobic Interactions in the Trivaline–Water System. J. Phys. Chem. B, 122, 2018, 4289-4298, doi: 10.1021/acs.jpcb.8b00833 The paper discusses how the backbone is solvated in trivaline peptides, when adopting ?-conformation and polyproline-II helix.