Let $X$ be a variety -- one can compute $\text{Pic}(X) = H^1(X, \mathcal{O}^*_X)$ by choosing a Cech cover which is acyclic with respect to $H^\bullet(-, \mathcal{O}^*)$.
Can one always do this? It seems to me that the answer is no. For example, take the quadric cone $X = \text{Spec} k[x,y,z]/xy-z^2$. $\text{Pic}(X)$ is generated by the two rulings, and it seems like there isn't a distinguished open containing zero which cuts out a ruling. Does this sound correct?
Are there known characterizations for when it's possible to find such a Cech cover?