Developing drug like molecules targeting protein-protein interactions is one of the main goals of current medicinal chemistry. To drive the design process it is fundamental to locate those sites on the protein-protein contact surface that are more critical for protein binding, which are the most eligible targets to affect the protein complex formation. In this work we show how computational alanine scanning can be used to identify such critical sites and evaluate their interactions with small molecules designed to inhibit the complex formation. Complex of protein IL2 with IL2R alpha and with some small molecule inhibitors are used as an example. (C) 2011 Elsevier B.V. All rights reserved.