QSAR Modeling: Where Have You Been? Where Are You Going To?

Quantitative structure−activity relationship modeling
is one of the major computational tools employed in medicinal
chemistry. However, throughout its entire history it has drawn
both praise and criticism concerning its reliability, limitations,
successes, and failures. In this paper, we discuss (i) the
development and evolution of QSAR; (ii) the current trends,
unsolved problems, and pressing challenges; and (iii) several
novel and emerging applications of QSAR modeling. Throughout
this discussion, we provide guidelines for QSAR development,
validation, and application, which are summarized in best
practices for building rigorously validated and externally
predictive QSAR models. We hope that this Perspective will
help communications between computational and experimental
chemists toward collaborative development and use of QSAR
models. We also believe that the guidelines presented here will help journal editors and reviewers apply more stringent
scientific standards to manuscripts reporting new QSAR studies, as well as encourage the use of high quality, validated
QSARs for regulatory decision making.