Table 1 Description of the topography of the energy surface in φ, ψ space with remarks concerning the secondary structure preferences for each residue type

−72° < φ < − 60°

−45° < ψ = − 39°

−75° < φ < − 74°

−5° < ψ < − 4°

−72° < φ < − 76° –145° < ψ < −144°

100° < φ < 180°

90° < ψ < 180°

A (Ala)

Ramachandran plot shows a classical pattern with −30° < φ < 30° forbidden zone. The β-strand and PP-helix are well populated while α-helix is not strongly favoured. The right-hand region which is fully accessible to glycine (see G) is weakly accessible to A compared to other (non-G) amino acid types

C (Cys)

Very similar to A, but an additional forbidden zone shows up on the far right (φ ≈ 152°). Like A, β-strand and PP-helix are well populated while α-helix is not strongly favoured

D (Asp)

Very similar to C the right-hand forbidden zone broader now due to the bulk of the side chain carboxylate moiety. PP-helix and 3₁₀ helix preferring rather than the “more famous” α-helix and β-strand.

E (Glu)

Very much like D except now the α-helix comes more into prominence (polyglutamate or glutamate-rich peptides are known to favour the α-helix). E also has a side chain carboxylate moiety but it is displaced further away from the peptide chain by an additional methylene, so the forbidden band is narrower than that for D

F (Phe)

Even distribution amongst all secondary structure types but very reminiscent of E. F is likewise known to favour the α-helix. Strongly forbidden 120° < φ < 152° region due to bulky aromatic side chain

G (Gly)

Essentially symmetrical distribution about the universal −30° < φ < 30° barrier. β-strand and PP-helix dominate. G can occur within α-helices but this residue type uniquely does not favour the standard right-handed geometry over a left-handed one, both isomers are equally possible [for A that would be an extremely rare event (but not unknown)]. Because of its rotational flexibility G is an important turn motif

H (His)

Similar to F but now with α-helix not strongly favoured. But like F has a very prominent 120° < φ < 152° restricted region

I (Ile)

This residue type offers a major difference to most of the others. A “new” restricted region −120° < ψ < −140° appears, indicative of significant steric clashes due to β-branching [NB. In this context “β” means that the branching occurs at the CB atom, as with T and V (qv)]. As for the allowed regions, the polyproline region φ = −72°, ψ = 144° is evident while the α-helix region φ = −72°, ψ = −45°, is considerably eroded (this was already reported in Bywater and Veryazov 2013 and similar findings were reported recently in Ilawe et al. 2015). The β-strand region shows up very prominently. This is as expected from experimental data (Bellesia et al. 2010; Hovmoller et al. 2002). We put the ranking for this residue type in the order polyproline > α-helix ∼ β-strand ≫ 3₁₀ helix

K (Lys)

Resembles E in many ways but now there is a clear gap between the β-strand/PP-helix region and the (favoured) α-helix region. The 3₁₀ helix region seems to be excluded (this may have significance for protein folding since 3₁₀ helices can play a role in this process). One very striking feature, with it shares only with S (see below) is that the large barrier to rotation of the φ angle (usually 120° < φ < 152°) is shifted to φ ≈ 108°

L (Leu)

Similar to C and distinctly different from its position isomer I (qv). The absence of the −120° < ψ < −140° steric clash accounts for the different secondary structure propensities between L and I. In particular, L is amenable to the α-helix geometry while I is not. L does not seem to favour the PP-helix, and the β-strand region and α-helix regions are discontiguous

M (Met)

M is similar to F. For example, it is “α-helix friendly”. The 120° < φ < 152° forbidden zone shows up prominently. This restricted zone is due to the bulkiness of the side chain [in the interior of proteins, M often “behaves like” F (and W, Y) due partly to this bulkiness but also due to quantum chemical considerations concerning the somewhat similar behaviour of d-orbitals compared with the π-orbitals of aromatic side chains. These allow opportunities for orbital overlap which confers directionality]

N (Asn)

N is similar to D favouring the PP-helix and 3₁₀ helix rather than the more famous α-helix and β-strand. But, while D is not regarded as being “α-helix preferring” exactly, N has a an even greater aversion and can be considered “α-helix forbidding”. The only difference between N and D is the amido-terminal group of the side chain instead of a carboxylate

P (Pro)

The plot for P is necessarily restricted to a very narrow strip in the Φ dimension due to its cyclic structure. As expected, P favours PP-helix almost by definition. But α-helix is a good runner-up. The notion that P is “helix-breaking” needs to be revised. P can sit at the beginning of an α-helix and even in the middle of such a helix (Bywater et al. 2001), although there will be disruptions at the (i − 3)rd residue (so-called “kinks”). But for P (where only the −60° < Φ < −72° region is relevant for this residue type (see Fig. 5) one can clearly discern the order of preference as PP-helix > α-helix ⋙ anything else

Q (Gln)

One might expect this to be similar to E. But it isn’t. Compared to E there is almost no preference for α-helix. This has to be a most significant result. How can amidation of a side chain make such a difference? But it mirrors exactly the difference between N and D

R (Arg)

One might expect R to resemble K. But, unlike K there is no divide between the α-helix and the PP-helix/β-strand region. These areas are effectively contiguous and 3₁₀ helices would be accessible

S (Ser)

One might expect S to be similar to C (qv) but it isn’t. There is a much more pronounced 36° < φ < 136° zone and α-helix propensity is greatly diminished. The explanation probably has to do with intraresidue hydrogen-bonding. As noted with K (q.v.) the φ rotation barrier is shifted, this time to ≈96°

T (Thr)

Similar to S in the 36° < φ < 136° zone and almost exactly like I (and V) (qv) in the −120° < ψ < −140° region, indicative of significant β-branching causing steric clashes. Enhanced α-helix propensity compared with S

V (Val)

As with I and T: the −120° < ψ < −140° region highly restricted. Greatly diminished α- and 3₁₀ helix propensity, β-strand dominant. An interesting incursion into the −80° < ψ < −120° region not really seen with any other residue types

W (Trp)

Very similar to H (and Y, F, M) due to bulky side chain

Y (Tyr)

Very similar to H (and W, F, M) due to bulky side chain