  Automatic Chemical Design is a framework for generating novel molecules with
optimized properties. The original scheme, featuring Bayesian optimization over
the latent space of a variational autoencoder, suffers from the pathology that
it tends to produce invalid molecular structures. First, we demonstrate
empirically that this pathology arises when the Bayesian optimization scheme
queries latent points far away from the data on which the variational
autoencoder has been trained. Secondly, by reformulating the search procedure
as a constrained Bayesian optimization problem, we show that the effects of
this pathology can be mitigated, yielding marked improvements in the validity
of the generated molecules. We posit that constrained Bayesian optimization is
a good approach for solving this class of training set mismatch in many
generative tasks involving Bayesian optimization over the latent space of a
variational autoencoder.
