Retrospective: 12 years of antigenic determinant predictions, and more

The Hopp and Woods hydrophilicity method for locating antigenic determinants was published in 1981. In the years since then, the method has been used widely and has played a vital role in many antigenic structure studies. The method has been criticized occasionally and replacements for it have been proposed. However, at this time, the Hopp and Woods method remains a method of choice for identifying antigenic sites and other protein interaction sites, because it has a higher success rate than other similar methods. Key to the success of this method is its cautious approach to charge-charge interactions, giving equal weight to positively and negatively charged residues, whereas other methods tend to favor one or the other. It has become clear that sites chosen by our method tend to be highly exposed, charged regions of the protein's surface which project into the environment and therefore have ample opportunity to contact other proteins. We have been exploring new uses for the method, and have found some applications in locating sites for other types of interactions, including those with other macromolecules such as DNA and RNA. It seems likely that this simple and reliable procedure will continue to find use in predicting the locations of major antigenic epitopes, and may also find use as a general prediction method to identify interaction sites on proteins that make charge-dependent contacts with a variety of other biological macromolecules.