sentences:  Drug discovery has been through periods when drug candidates that bind covalently to their targets are attractive and then are avoided; the success of bortezomib made boron-based covalently binding candidates more attractive in the late 2000s.In order for the complex to be stable, the free energy of complex by definition must be lower than the solvent separated molecules.The binding may be primarily entropy-driven (release of ordered solvent molecules around the isolated molecule that results in a net increase of entropy of the system).