Bioinformatics An Introduction 4th Edition (Jeremy Ramsden)

228

The Molecules of Life

Glycoproteins, which may be very large, such that they form gels by entanglement.

The polypeptide backbone is extensively decorated with relatively short polysac-

charides. Typically they act as lubricants and engulfers (example: mucin);

Membrane proteins, which

are

also

globular,

but

permanently

embedded

(transversally) in a lipid bilayer membrane. They mainly function as channels,

energy and signal transducers, and motors (examples: ATPase, bacteriorhodopsin,

and porin).

15.5.1

Amino Acids

The basic structure of an amino acid is HSubscript 22N–CSuperscript left parenthesis alpha right parenthesis⁽^α⁾HR–COOH. At physiological pH,

amino acids exist in zwitterionic form, HSubscript 33NSuperscript plus⁺–CSuperscript left parenthesis alpha right parenthesis⁽^α⁾HR–COOSuperscript minus⁻. R denotes the vari-

able side chain (residue); except for glycine (R = H), the CSuperscript left parenthesis alpha right parenthesis⁽^α⁾is asymmetric and

hence chiral. The different residues are listed in Table 15.6.

Problem. Compare the abundances given in Table 15.6 with those predicted from

Table 7.1, assuming that each nucleic acid triplet occurs with equal probability.

Amino acid polymerization takes place via elimination of water and the forma-

tion of the so-called peptide bond. Hence, a tripeptide with residues RSubscript 11, RSubscript 22, and RSubscript 33

has the structure HSubscript 22N–CSuperscript left parenthesis alpha right parenthesis⁽^α⁾HRSubscript 11–CO–N–CSuperscript left parenthesis alpha right parenthesis⁽^α⁾HRSubscript 22–CO–N–CSuperscript left parenthesis alpha right parenthesis⁽^α⁾HRSubscript 33–COOH. Amino

acids polymerized into a polypeptide chain are usually called peptides. The CO–N

bond is in resonance with the C=O bond and is therefore rigid, the CO–N triatom

system being planar; but the N–CSuperscript left parenthesis alpha right parenthesis⁽^α⁾and CSuperscript left parenthesis alpha right parenthesis⁽^α⁾HRSubscript 11–CO bonds are free to rotate inde-

pendently. Two dihedral angles,phiφ andpsiψ respectively, per amino acid therefore sufﬁce

to completely characterize the conformation of a polypeptide chain. A Ramachan-

dran plot ofpsiψ versusphiφ can be constructed for each amino acid showing the allowed

conformations; constraints arise due to the overlaps between the atoms attached to

the N–CSuperscript left parenthesis alpha right parenthesis⁽^α⁾–C backbone.⁹

The amino acids can be classiﬁed in several ways according to their residues.

A binary classiﬁcation groups them as apolar (incapable of hydrogen-bonding) or

polar (see Fig. 15.6). The polar residues can be further classiﬁed into net hydrogen

bond donors and acceptors. Other binary classiﬁcations are electrostatically charged

(ionizable) and uncharged; big and small; and glycine or not.

15.5.2

Protein Folding and Interaction

Proteins are synthesized in vivo by the consecutive addition of amino acids to form

an elongating peptide chain with the conformation of a random coil in the aqueous

9 Another kind of Ramachandran plot is used to represent the structure of an entire polypeptide

chain, by plotting the actual values ofpsiψ versusphiφ in the folded structure of each amino acid.