Soluble guanylyl cyclase (sGC) is one of the key enzymes involved in many fundamental biological processes including vasodilatation. It can be allosterically activated by synthetic compound such as YC-l. Recently, the 3D structure of adenylyl cyclase (AC), which is a homologue of sGC, was determined. Using AC as template and homology modeling, the 3D structure of sGC is predicted. Prior experimental work has suggested two binding modes of YC- 1. In the current investigation, molecular dynamics simulations (MD) were conducted to seek more detail of molecular mechanism of sGC activation.

From these MD simulations, a tentative mechanism of sGC activation is established. The difference in the initial binding modes of YC-l in its binding pocket results in different conformational changes in the active site of sGC, which results in different catalytic capability. Meanwhile, YC-l was found to be strongly attracted to α₁ CYS594, a residue deep inside of the allosteric binding pocket.