Before revision:  While initially epistatic interactions are likely to constrain the evolvability of a protein, we find no evidence that the HIV-1 protease has reached its potential for adaptation after 9 years of adapting to a changing drug environment . The protein is able to encode information about novel and more potent drugs using epistatic interactions, while maintaining sufficient diversity and thermostability. We propose that this mechanism is central to protein evolution not just in HIV-1 protease, but for any protein adapting to rapidly changingconditions
After revision:  While initially epistatic interactions are likely to constrain the evolvability of a protein, we find no evidence that the HIV-1 protease has reached its potential for adaptation after 9 years of adapting to a drug environment that itself is constantly changing.