Publisher Summary This chapter deals with the recent developments regarding the description and nature of the conformation of proteins and polypeptides with special reference to the stereochemical aspects of the problem. This chapter considers the parameters that are required for an adequate description of a polypeptide chain. This chapter focuses the attention on what may be called “internal parameters”—that is, those which can be defined in terms of the relationships among atoms or units that form the building blocks of the polypeptide chains. This chapter also provides an account of the mathematical method of utilizing these parameters for calculating the coordinates of all the atoms in a suitable frame of reference, so that all the interatomic distances, and bond angles, can be calculated and their consequences worked out. This chapter observes conformations in amino acids, peptides, polypeptides, and proteins.

Conformation of Polypeptides and Proteins

Publisher Summary The vibrational spectrum of a molecule is determined by its three-dimensional structure and its vibrational force field. An analysis of this (usually infrared (IR) and Raman) spectrum can therefore provide information on the structure and on intramolecular and intermolecular interactions. The more probing the analysis, the more detailed is the information that can be obtained. Detailed analyses of the vibrational spectra of macromolecules, however, have provided a deeper understanding of structure and interactions in these systems. An important advance in this direction for proteins came with the determination of the normal modes of vibration of the peptide group in N-methylacetamide, and the characterization of several specific amide vibrations in polypeptide systems. Extensive use has been made of spectra-structure correlations based on some of these amide modes, including attempts to determine secondary structure composition in proteins. Polypeptide molecules exhibit many more vibrational frequencies than the amide modes. Over the years, some normal-mode calculations have provided greater insight into the spectra of particular molecules. However, these have often been based on approximate structures or have employed limited force fields. These force fields can now serve as a basis for detailed analyses of spectral and structural questions in other polypeptide molecules. The aim of this chapter is to present these recent developments in the vibrational spectroscopy of peptides, polypeptides, and proteins.

Vibrational spectroscopy and conformation of peptides, polypeptides, and proteins.

Common core structure of amyloid fibrils by synchrotron X-ray diffraction.

Publisher Summary The chapter reviews the results obtained from measurements of hydrogen exchange (H–H, H–D, and H–T) in proteins and related compounds. The slowness of the rate of hydrogen exchange in a protein, relative to the exchange rate observed with simple peptides under the same experimental conditions is closely related to the conformation of the protein molecule in aqueous solution. Quantitative measurements of the rate of hydrogen exchange in a given protein, under specified experimental conditions, provide a multiparameter characterization of the protein conformation (or distribution of conformations) present under these conditions. Moreover, the chapter discusses the experimental techniques that have been used to measure quantitatively the rate of hydrogen exchange. The chapter also discusses arguments that support case, as the mechanism of exchange of the slowly exchanging hydrogen atoms.

Hydrogen exchange in proteins.

Amide modes and protein conformation.

The structure of the ω-form of poly-β-benzyl-L-aspartate

A number of polymers and copolymers containing $\beta$-benzyl-L-aspartate has been prepared and their optical rotatory dispersion in a variety of solvents has been measured. The results of these measurements together with studies of infra-red spectra, X-ray diffraction patterns, deuteration rates and molecular models lead to the following conclusions. (i) The $\alpha$-helical form of poly-$\beta$-benzyl-L-aspartate is considerably less stable relative to the solvated randomly coiled form than that of poly-$\gamma$-benzyl-L-glutamate. (ii) The left-handed $\alpha$-helix of poly-$\beta$-benzyl-L-aspartate is more stable than the right-handed one. (iii) The difference in stability between the two senses of $\alpha$-helix is much less in the case of poly-$\beta$-benzyl-L-aspartate than in that of poly-$\gamma$-benzyl-L-glutamate or poly-L-alanine.

The Stability and Screw Sense of the α-Helix in Poly-β-Benzyl-L-Aspartate

The “Cross-β” structure in polypeptides of low molecular weight

IN Moffitt's expression for the variation of the optical rotation of an L-polypeptide in the α-helical form with wave-length1,2, the constant b
0 has been found to have values between − 400 and − 700 deg. cm.2/decimole; the negative value is certainly associated with a right-handed screw sense in poly-L-alanine3. Recently, values up to 631° have been reported for poly-β-benzyl-L-aspartate ([CO.NH.CHCH2CO.OCH2C6H5]n) in chloroform solution by Blout and Karlson4. This positive value of b
0 may indicate either the ‘structural’ anomaly of a left-handed screw sense, or alternatively an ‘optical’ anomaly due to interaction between peptide and side-chain chromophores or consequent upon some minor structural peculiarity. We have confirmed the anomalous result and have examined the polymer by a variety of techniques.

alpha-Helices and a new polypeptide fold in poly-beta-benzyl-L-aspartate.

The optical rotations of a number of synthetic polypeptides have been measured in a variety of solvents. For each polypeptide species, a number of copolymers of different D:L compositions have been examined. Several distinct types of behaviour have been found, which may readily be interpreted in terms of the relative stability of left-handed helices, right-handed helices, and random coils. In solvents that are not too polar (even for quite considerable departures from the enantiomorph) predominantly L polymers exist entirely as right-handed helices. The rotation of a right-handed helical form of several meso polypeptides has been deduced; this rotation varies somewhat from polymer to polymer but is not markedly dependent on the solvent. It appears that the solvated D and I residues on a meso helical polypeptide largely cancel out each other’s contributions to the rotation. The dispersion of the right-handed helical form of poly-DL-leucine has been derived.

A. R. Downie

Papers

The structure of the ω-form of poly-β-benzyl-L-aspartate

The Stability and Screw Sense of the α-Helix in Poly-β-Benzyl-L-Aspartate

The “Cross-β” structure in polypeptides of low molecular weight

alpha-Helices and a new polypeptide fold in poly-beta-benzyl-L-aspartate.

The Optical Rotation and Molecular Configuration of Synthetic Polypeptides in Dilute Solution