Conformation of Biological Molecules

The determination of the three-dimensional structure of a biological molecule is the starting point in the understanding of molecular mechanisms involved in its complex biochemical reactions. The molecular architecture of multimolecular systems such as membranes and chromosomes provides the key to the fascinating field of molecular biology. Stereochemical details of biological macromolecules and their interactions with pharmacological agents form the basis for drug design. Naturally, the study of the structure and function of biological molecules has aroused tremendous interest and investigations in this area are being carried out in a large number of laboratories. The techniques used for this purpose include both experimental methods (X-ray and neutron diffraction measurements, study of NMR, ESR, vibrational and electronic spectra, ORD, CD and dipole moment measurements, biochemical modifications etc. ) and the oretical methods (quantum mechanical and classical potential energy calculations, Monte Carlo simulations and molecular graphics). F or several years now, X-ray diffraction [1] has served as our only source of infor mation on the three-dimensional arrangements of atoms in biopolymers. Fiber-diffrac tion of DNA led to the proposal of the DNA double helix. Fibers of long~hain polymers show ordering in the direction of the fibre-axis but not in the transverse plane. Accurate estimates of the dimensions of helical structures can be made using techniques on the basis of which models of biopolymers can be constructed.

Contenu
1 General Theory.- 1.1 Introduction.- 1.2 What is Conformation?.- 1.3 Conformational Theory.- 1.4 Structure of Long-Chain Polymers.- 1.5 Problems in NMR Studies of Biological Molecules.- 2 NMR Techniques in Conformational Studies.- 2.1 Coupling Constants.- 2.2 Chemical Shifts of Hydrogen-Bonded Protons.- 2.3 Magnetic Anisotropy of Chemical Bonds or Groups.- 2.4 13C Chemical Shifts.- 2.5 31P Chemical Shifts.- 2.6 Relaxation Times (T1 and T2).- 2.7 Nuclear Overhauser Effect.- 2.8 Paramagnetic Reagents.- 2.9 Use of Liquid Crystals as Solvents.- 2.10 Deuterium Quadrupole Coupling Constants.- 2.11 Solvent Accessibility.- 2.12 From NMR Parameters to Spatial Structures.- 3 Nucleosides, Nucleotides and Nucleic Acids.- 3.1 Description of Nucleotide Structures.- 3.2 Glycosidic Bond Rotations.- 3.3 Sugar Ring Conformation: Pseudorotation.- 3.4 Backbone Angles.- 3.5 NMR Studies on Nucleosides.- 3.6 Small Nucleotides.- 3.7 Dinucleoside Phosphates and Short Segments of Nucleic Acids.- 3.8 Random-Coil Polynucleotides.- 3.9 Helical Polynucleotides.- 3.10 t-RNA.- 3.11 Drug-Nucleic Acid Interactions.- 4 Amino Acids, Peptides and Proteins.- 4.1 Description of the Structure of Peptide Units.- 4.2 Theoretical Considerations. The ø, ? Maps.- 4.3 NMR Techniques in the Study of Peptide Conformations.- 4.4 Conformations of Amino Acids.- 4.5 Linear Peptides.- 4.6 Cyclic Peptides.- 4.7 Homopolymeric Peptides. Helix-Coil Transition.- 4.8 Characterization of Protein Structures by NMR.- 4.9 Protein-Nucleic Acid Interaction.- 5 Polysaccharides.- 5.1 Structures of Polysaccharides and Carbohydrates.- 5.2 Conformations of Monosaccharides.- 5.3 Conformations of Polysaccharides.- 5.4 Glycoproteins and Peptide-Carbohydrate Interactions.- 6 Lipids and Molecular Organization in Membranes.- 6.1Biomembranes.- 6.2 General Properties of Phospholipids.- 6.3 Conformations of Phospholipids.- 6.4 Membrane Organization and Fluidity.- 6.5 Lipid-Protein and Lipid-Cholesterol Interactions.- 7 Acknowledgements.- 8 References.- 9 Appendix.- 10 Subject Index.