The present invention provides methods to characterize the structure, stability, and intersubunit interfaces between the matrix, capsid, and nucleocapsid domains of the Gag polyprotein during HIV capsid assembly and maturation. A method of screening for compounds that promote or inhibit viral assembly and maturation is disclosed. A novel mass spectrometry based approach to measure hydrogen/deuterium exchange profiles is also disclosed. Quantitative data resulted from these studies may lead to well defined capsid assembly assays that can be adapted for rapid antiviral drug screening.