This is the first of the last three chapters on proteins, which are the workhorses in the cell. The most fundamental property of a protein is its isoelectric point (pI), which determines what cellular components a protein can interact electrostatically with (e.g., a positively charged substrate would demand a negatively charged enzyme). This chapter first explains the iterative approach to computing theoretical protein pI and then applies it to a study of genomic adaptation of Helicobacter pylori, a bacterial gastric pathogen, to the acidic environment of mammalian stomach. Two research questions are addressed. How did H. pylori acquire its proteins with extraordinarily high pI? Do these proteins with high pI contribute to the acid resistance of the pathogen? A detailed genomic analysis illustrates the hypothesis-driven approach in science.