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The aqueous environments both inside and surrounding animal cells profoundly affect the structure and function of molecules and membranes. Solutes dissolved in water are surrounded by a shell of water molecules. The polarity of the water molecules in the shell is determined by the solute's ionic charge. The structure of proteins is profoundly affected by the activity of the water in which they reside, and by the types and quantities of ions present. The interactions of lipids with water are dominated by hydrophobic interactions. These interactions dictate the structure of membranes, and influence the locations and functions of proteins associated with membranes. The lipid bi-layer acts as a powerful barrier to trans-membrane movements. Proteins sited within the membrane can therefore play important roles as channels and transport moieties.

Modeling of sequence evolution is fundamental to ancestral sequence reconstruction. Care must be taken in choosing a model, however, as the use of unrealistic models can lead to erroneous conclusions. The choice of model and the effects of assumptions inherent within are discussed in this chapter in terms of their effects on probabilistic ancestral sequence reconstruction. This chapter discusses standard probabilistic models, site rate variation to these models, and deviations from the standard (homogeneous, stationary, reversible) models. Model selection, selecting one model from many, given data, and the comparison of different models are included as well as covarion models, the use of outside information when modeling, and the treatment of gaps.

A growing body of evidence points to the existence of genotype networks in both protein and RNA phenotypes, and to their importance for evolutionary innovation. This evidence comes from comparative analysis of protein and RNA genotypes and phenotypes, from laboratory evolution experiments, and from computational analysis of RNA and model protein structures. This evidence shows that many genotypes can form the same phenotype, even for molecules of modest size. They form vast connected networks of genotypes that often nearly span genotype space. This means that two molecules with the same phenotype may share little or no sequence similarity. A series of mutational changes on a genotype network can preserve a phenotype while exploring an ever-changing spectrum of new phenotypes. Laboratory evolution experiments show that these properties facilitate the evolution of new functions by allowing exploration of new phenotypes, while leaving an existing phenotype unchanged.

This chapter analyses the three-dimensional structure of proteins represented as residue networks. It starts by introducing the structure of proteins and how protein residue networks can be constructed. The chapter then reviews the topics of small-worldness and scale-freeness of residue networks, followed by an analysis of the centrality of amino acids in residue networks and the relationship between closeness centrality and the atomic vibrations produced by thermal fluctuations in proteins. The topological atomic displacements are used to identify regions of small and large packing in proteins; the use of closeness is presented as a tool for identifying enzyme binding sites. The global topological properties of residue networks are presented. The chapter concludes with an analysis of the universality in the topological structure classes of residue networks and the role of holes identification in detecting protein binding sites.

This chapter explores the role of databases in scientific knowledge-making using one prominent example: GenBank. Biological databases, organized with computers, cannot be thought of as just collections. Instead, biological databases are orderings of biological materials. They provide ways of dividing up the biological world; they are tools that biologists use and interact with. Databases store information within carefully crafted digital structures. Computer databases construct orderings of scientific knowledge: they are powerful classification schemes that make some information accessible and some relationships obvious, while making other orderings and relationships less natural and familiar. Organizing and linking sequence elements in databases can be understood as a way of representing the connections between those elements in real organisms. The database becomes a digital idealization of living system, emphasizing particular relationships between particular objects.

Chapter 1 reviews basic principles of protein structure—the nature of proteins as polymers of amino acids, the variety of amino acids, and the way in which the physicochemical properties of amino acid side chains influence the folding of a polymer into a three-dimensional protein with specific functional properties. Whereas the main chain polypeptide is linked together by covalent bonds, the three-dimensional structure of native state proteins is mainly stabilized by a multitude of noncovalent, weakly polar interactions. After securing the base camp with this brief overview of protein structure, the subsequent chapters explore the functional properties of hemoglobin, the biophysical mechanisms underlying such properties, and the physiological role of hemoglobin in respiratory gas transport.