|
Abstract
|
HIV-1 protease (PR) is a major drug target in combating AIDS, as it plays a key role in maturation and replication of the virus. All of drugs designed to inhibit enzyme activity by blocking the active site, which exists only in the dimer. An alternative inhibition mode would be required to overcome the emergence of drug resistance through the accumulation of mutations. This might involve
inhibiting the formation of the dimer itself. Here, the folding of HIV-1 PR is studied with two simulation models appropriate for folding mechanism studies. All-atom molecular dynamics simulations strongly support the stability of an isolated monomer. Accordingly, the design of dimerization inhibitors should not focus only on the flexible N and C termini that constitute most of the dimer interface, but also on other structured regions of the monomer.
|