title: Modeling a crowdsourced definition of molecular complexity.
abstract: This paper brings together the concepts of molecular complexity and crowdsourcing. An exercise was done at Merck where 386 chemists voted on the molecular complexity (on a scale of 1-5) of 2681 molecules taken from various sources: public, licensed, and in-house. The meanComplexity of a molecule is the average over all votes for that molecule. As long as enough votes are cast per molecule, we find meanComplexity is quite easy to model with QSAR methods using only a handful of physical descriptors (e.g., number of chiral centers, number of unique topological torsions, a Wiener index, etc.). The high level of self-consistency of the model (cross-validated R(2) ∼0.88) is remarkable given that our chemists do not agree with each other strongly about the complexity of any given molecule. Thus, the power of crowdsourcing is clearly demonstrated in this case. The meanComplexity appears to be correlated with at least one metric of synthetic complexity from the literature derived in a different way and is correlated with values of process mass intensity (PMI) from the literature and from in-house studies. Complexity can be used to differentiate between in-house programs and to follow a program over time.
authors.affiliation: Structural Chemistry, Merck Research Laboratories, Merck & Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065, United States.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Sheridan
authors.forename: Nicolas
authors.initials: N
authors.lastname: Zorn
authors.forename: Edward C
authors.initials: EC
authors.lastname: Sherer
authors.forename: Louis-Charles
authors.initials: LC
authors.lastname: Campeau
authors.forename: Charlie Zhenyu
authors.initials: CZ
authors.lastname: Chang
authors.forename: Jared
authors.initials: J
authors.lastname: Cumming
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Maddess
authors.forename: Philippe G
authors.initials: PG
authors.lastname: Nantermet
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sinz
authors.forename: Paul D
authors.initials: PD
authors.lastname: O'Shea
mesh_terms: D063045:Crowdsourcing; D062126:Databases, Chemical; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013237:Stereoisomerism