Integrating computational lead optimization diagnostics with analog design and candidate selection

Abstract

Aim:

Combining computational lead optimization diagnostics with analog design and computational approaches for assessing optimization efforts are discussed and the compound optimization monitor is introduced.

Methods:

Approaches for compound potency prediction are described and a new analog design algorithm is introduced. Calculation protocols are detailed.

Results & discussion:

The study rationale is explained. Compound optimization monitor diagnostics are combined with a thoroughly evaluated approach for compound design and candidate prioritization. The diagnostic scoring scheme is further extended.

Future perspective:

Opportunities for practical applications of the integrated computational methodology are described and further development perspectives are discussed.

Lay abstract

Compound optimization is a central task in medicinal chemistry, which has many potential pitfalls. Computational approaches that help to better understand and guide chemical optimization efforts are highly desirable, but only a few are currently available. We have aimed to develop a computational methodology that combines, for the first time, the evaluation of progress in chemical optimization with the design of new candidate compounds.

Graphical abstract