Introduction

Abstract

This introductory chapter deals with protein structure and its synthesis The 20 α-amino-acids that compose proteins are all of the L-configuration except for glycine that is optically inactive. That a protein is a chemically pure entity was proven by Sumner in crystals of the enzyme urease. A protein molecule is defined by the size/weight of a linear polypeptide that composes it. A fundamental method of structure solution of molecules is X-ray diffraction. When applied to peptides by Pauling and Corey it supplied information about the distances between atoms and showed that the peptide bond is planar. First proteins whose structure was solved were myoglobin and haemoglobin followed by the enzymes lysozyme and chymotrypsin. The bottleneck in determining a protein structure from its diffraction intensity maxima was lack of knowledge of the phase of diffracted X-rays. This was surmounted by various techniques that go under names like MIR, MAD, SIRAS and others. Solution of a protein structure involves calculation of an enormous quantity of numerical data in the refinement and production of the electron density of the molecule. The resolution to which structure of proteins has been solved, around 2 Å, bears no comparison to 0.01 Å obtained for small molecules. All these calculations demand extensive use of computer programs. Binding-sites endow proteins with unique selectivity to small molecules and are physiologically important. The forces responsible for the binding of small molecules to binding-sites are discussed.