Hsp90, while in the open conformation, leaves some hydrophobic residues exposed, to which unfolded and misfolded proteins that have unusual hydrophobic regions exposed are recruited with high affinity. When a bound substrate is in place, the energy-releasing ATP hydrolysis by the ATPase function near the N-terminal domain forces conformational changes that clamp the Hsp90 down onto the substrate. In a reaction similar to that of other molecular clamp proteins like GyrB and MutL, this site drives virtually all of the protein folding functions that Hsp90 plays a role in. In contrast, MutL and GyrB function as topoisomerases and use a charge clamp with a high amount of positively charged sidechains that is electrostatically attracted to the negative backbone of DNA.