An algorithm for isoelectric point estimation

One of the most common techniques for separating mixtures of proteins is the two-dimensional polyacrylamide gel. In these gels, proteins are separated in one dimension based on their electromigration speeds through the gel (roughly determined by their molecular weights) and in another dimension by the pH at which their side chains cumulatively amount to a neutral charge, called the isoelectric point. As a result, it is often useful to know the molecular weight and isoelectric point values for a protein. Both of these values can be estimated from the protein sequence. These estimates are not generally exact because many proteins are chemically modified after they are assembled by ribosomes, sometimes leading to mass or charge differences in the final protein product. Molecular weights (MW) are simple to calculate. The masses for the amino acids in the protein are first summed, and then the mass of water is added. If any modifications to the protein structure are known, these masses should be added to the sum as well. One common modification clips the first amino acid from the protein (usually a methionine due to the way in which protein sequences are encoded by DNA). By summing together all the masses for the elements of the protein, the mass for the whole is calculated. Isoelectric point (pI), on the other hand, is a more complex value to calculate for proteins. Generally, pI is defined as the pH at which a protein takes on a net negative charge. Proteins usually have many different ionizable groups in their structures, and so some parts may take on a negative charge while others take on a positive charge. At a particular pH, an individual amino acid’s side chain will have some probability for adopting either a positive, neutral, or negative