Hydrogen Bonding in Proteins and Nucleic Acids

The modern concepts of protein structure and of the H bond had their genesis about the same time, and have advanced together. Hydrogen bond theory began to flourish soon after Latimer and Rodebush presented their classical paper (1201), and x-ray diffraction methods were applied to proteins about the same time. Twenty years later, IR spectroscopy studies were begun. In this chapter we shall show the crucial role of the H bond in modern proposals for protein structures, but the treatment will be restricted to those phases of protein study which reveal this role. (Of course, such restriction dictates only passing mention of 

A protein molecule is a long chain (several hundred or thousand atoms) of condensed a-amino acid molecules (called residues) arranged in rather orderly fashion along the main chain but with various types of branch chains and, in some cases, crosslinking. The general representation of a residue is given in Fig. 

Here is a word picture that supplies a mental hook for remembering the levo configuration (for a-amino acids only). Visualize yourself on the N atom at the foot of an arch over C to and passing between the other two bonds to C . As you walk over the arch, the C==0 group is on your lejt (levo) side. 

In natural proteins the residues are from a group of about 20 acids— all in the L (levo) configuration, except glycine in which R = H. [Sanger and Smith list these acids and the abbreviations used (1785).] Apparently some D (dextro) acids occur in certain lower forms of life. They will be ignored here, although d acids are gaining importance, as revealed 

FIGURE 10-1 Schematic diagram of a levo a-amino acid residue. 

---

Recent developments in the direct observation of J couplings across hydrogen bonds in proteins and nucleic acids provide additional information for structure and function studies of these molecules by NMR spectroscopy. Yan et al proposed a modified J(N,N)-correlated TROSY experiment... 

Wavefunction s Spartan Student Edition (6) is used extensively in this course for building molecules and visualizing molecular shape, polarity, intermolecular interactions, hydrogen bonding, solubility, protein and nucleic acid structure. Spartan exercises are used to investigate the connection between the structure and shape of water and its polarity, intermolecular interactions, and... 

Even though these intramolecular hydrogen bonds are relatively weak ( 5 kcal/mol) they are critically important. For example, life as we know it is clearly not possible without water and there would be no liquid water without hydrogen bonds. Moreover, hydrogen bonds are used to mainttun the proper structures in proteins and nucleic acids, polymeric structures essential to our existence that we will meet later in this book. 

R 163 D.A. Case, NMR Parameters in Proteins and Nucleic Acids , p. 341 R 164 J.E. Del Bene, Characterizing Two-Bond NMR C- N, N- N, and Spin-Spin Coupling Constants Across Hydrogen Bonds... 

When thinking about chemical reactivity, chemists usually focus their attention on bonds, the covalent interactions between atoms within individual molecules. Also important, hotvever, particularly in large biomolecules like proteins and nucleic acids, are a variety of interactions between molecules that strongly affect molecular properties. Collectively called either intermolecular forces, van der Waals forces, or noncovalent interactions, they are of several different types dipole-dipole forces, dispersion forces, and hydrogen bonds. 

Of central importance for the formation of a specific protein-DNA complex are hydrogen bonds. The H-bonds are clearly identifiable in high resolution structures. H-bonds occur where a H-bond donor and acceptor he with 0.27-0.31 nm of each other. Energetically most favorable is the hnear arrangement of the H-bond, with deviations from hnearity leading to a reduction in energy. This characteristic is responsible for the stereospecific orientation of H-bond acceptors and donors. The H-bond thus contributes significantly to the spatial orientation between protein and nucleic acid. 

Numerous weak, noncovalent interactions decisively influence the folding of macromolecules such as proteins and nucleic acids. The most stable macromolecular conformations are those in which hydrogen bonding is maximized within the molecule and between the molecule and the solvent, and in which hydrophobic moieties cluster in the interior of the molecule away from the aqueous solvent. 

---