The Conformation of Polypeptides and Proteins

FIGURE 9-8 Schematic diagram of a polypeptide chain showing hydrogen bonds and a disulfide bridge. 

One of the great triumphs of 20th century science was the determination of the structure of many proteins and DNA (deoxyri-bonecleic acid) by X-ray diffraction. The excitement of the times and a flavor of the work was captured in James Watson s wonderful book, The Double Helix. Log on to amazon.com and order a copy immediately We now turn our attention to some of the fruits of this work. 

Tertiary structure refers to how a single chain can be folded in on itself (globular proteins are usually tightly folded and look like a knotted up piece of string). Finally, quaternary structure refers to how different molecules can pack to form an organized unit. 

We have already discussed primary structure in terms of the general character of amino acids and some specific examples of amino acid sequences in certain proteins will be discussed later. Our attention now is focused on secondary structure, or conformation as we called it when we discussed synthetic polymers. There are a number of factors that afreet the conformation of a polypeptide chain and a lot can be learned initially by just focusing on two of these steric restrictions on bond rotations and the strong driving force for amide groups to hydrogen bond to one another. 

In 1951, Pauling and Corey published a landmark paper on the structure of polypeptide chains. Earlier X-ray diffraction work in the 1930s had revealed the characteristics of the peptide bond and studies of fibrous proteins suggested that helical and extended chain structures were probably present. Using 

---

Optical Rotation and the Conformation of Polypeptides and Proteins Peter Urnes and Paul Doty... 

The procedures and calculations described in this chapter provide considerable insight into the factors affecting the conformations of polypeptides and proteins. The computer programs for gramicidin-S, oxytocin, vasopressin, etc., can also be used for larger structures—of the size of ribonuclease and lysozyme—although the required computer time is considerably increased. 

Maigret, B., B. Pullman, and D. Perahia Molecular Orbital Calculations of the Conformation of Polypeptides and Proteins. II. Conformational Energy Maps and Stereochemical Rotational States of Aromatic Residues. Biopolymers 10, 107-128 (1971). 

Pullman, B., and A. Pullman. 1974. Molecular Orbital Calculations on the Conformation of Amino Acid Residues of Proteins, Adv. Protein Chem. 28, 347-526. Ramachandran, G. N., and V. Sasisekharan. 1968. Conformation Of Polypeptides And Proteins, Adv. Protein Chem. 23, 283—438. 

The properties of polypeptides and proteins are determined to a large extent by the chemistry of the side chain groups, which may be summarized briefly as follows. Glycine in a peptide permits a maximum of conformational mobility. The nine relatively nonpolar amino acids-alanine, valine, leucine, isoleucine, proline, methionine, phenylalanine, tyrosine, and tryptophan-serve as building blocks of characteristic shape. Tyrosine and tryptophan also participate in hydrogen bonding and in aromatic aromatic interactions within proteins. 

An enormous work done in the field of polypeptides and proteins by Scheraga and coworkers includes calculations of both conformational energies and enzyme-substrate interactions for this special class of compounds 11 "13 . This kind of calculations on host-guest systems is well documented elsewhere and is not considered within the scope of this article. 

Hydrophobic interactions are important in the aggregation of polymethine dyes [81] and in the stabilization of particular conformations of polypeptides and proteins in aqueous solution [222, 232]. They also play an important role in the biochemical com-plexation between an enzyme and a substrate [77, 78, 83, 84, 348]. 

In particular, we can now determine the main-chain conformation of various copolypeptides (and some proteins) in the solid state from the criso and labelled natural protein can be provided. As the relation between the nitrogen shielding and the structures (primary, secondary and higher ordered structures) is clarified in the future, we will be able to get more detailed information on the structure of polypeptides and proteins in the solid state. 

Dependent on the conformation of the polymer chains intra- or intermolecular hydrogen bonds may be encountered. Thus, the helix conformation of polypeptides and proteins is stabilized by intramolecular hydrogen bonds, while intermolecular hydrogen bonding occurs in the extended structure... 

AMINO ACIDS, PEPTIDES PROTEINS Recommended nomenclature and symbolism for amino acids and peptides J. Biol Chem. (1985) 260, 14-42 Biochemistry (1975) 14, 449-462 Abbreviations and symbols for the description of the conformation of polypeptide chains /. Biol Chem. (1970) 245, 6489-6497 Nomenclature of iron-sulfur proteins Eur. J. Biochem. (1979) 93, 427-430 Corrections Eur. J. Biochem. (1979) 102, 315 Nomenclature of peptide hormones J. Biol Chem. (1975) 250, 3215-3216 Nomenclature of human immunoglobulins Eur. J. Biochem. (1974) 45, 5-6 Recommended nomenclature of glycoproteins, glyco-peptides, and peptidoglycans /. Biol Chem. (1987) 262, 13-18 Recommended nomenclature of electron-transfer proteins... 

Very early examples in this area are the predictions that polyethylene should crystallize in a planar zig-zag conformation, poly(oxymethylene) in a helix having nine repeat units per live turns, some isotactic poly(a-olefins) in helices having three repeat units per single turn, and a number of polypeptides and proteins in the now-famous a-helices. All these predictions, and many others, have been confirmed experimentally.39... 

J. Moult and M. N. G. James. An algorithm for determining the conformation of polypeptide segments in proteins by systematic search. Proteins / 146-163 (1986). 

In addition to X-ray diffraction and NMR, which are direct techniques, methods based on the calculation of predicted three-dimensional structures of molecules in the range of 3 to 50 amino acids based on energy considerations are under rapid development. These approaches use what are commonly called molecular dynamics and energy minimization equations to specify the most probable conformation of polypeptides and small proteins. Often, when combined with information from other sources, such as X-ray crystallography or NMR studies, they have been demonstrated to be quite useful. However, when standing alone, their power and the accuracy of their predictive capability remains to be seen. 

---