title: Computer-aided design of carbon nanotubes with the desired bioactivity and safety profiles.
abstract: Growing experimental evidences suggest the existence of direct relationships between the surface chemistry of nanomaterials and their biological effects. Herein, we have employed computational approaches to design a set of biologically active carbon nanotubes (CNTs) with controlled protein binding and cytotoxicity. Quantitative structure-activity relationship (QSAR) models were built and validated using a dataset of 83 surface-modified CNTs. A subset of a combinatorial virtual library of 240 000 ligands potentially attachable to CNTs was selected to include molecules that were within the chemical similarity threshold with respect to the modeling set compounds. QSAR models were then employed to virtually screen this subset and prioritize CNTs for chemical synthesis and biological evaluation. Ten putatively active and 10 putatively inactive CNTs decorated with the ligands prioritized by virtual screening for either protein-binding or cytotoxicity assay were synthesized and tested. We found that all 10 putatively inactive and 7 of 10 putatively active CNTs were confirmed in the protein-binding assay, whereas all 10 putatively inactive and 6 of 10 putatively active CNTs were confirmed in the cytotoxicity assay. This proof-of-concept study shows that computational models can be employed to guide the design of surface-modified nanomaterials with the desired biological and safety profiles.
authors.affiliation: a Department of Chemistry , Bioinformatics Research Center, North Carolina State University , Raleigh , NC , USA .
authors.forename: Denis
authors.initials: D
authors.lastname: Fourches
authors.affiliation: b Laboratory for Molecular Modeling , Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina , Chapel Hill , NC , USA , and.
authors.forename: Dongqiuye
authors.initials: D
authors.lastname: Pu
authors.affiliation: c School of Chemistry and Chemical Engineering, Shandong University , Jinan , P.R. China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Li
authors.affiliation: c School of Chemistry and Chemical Engineering, Shandong University , Jinan , P.R. China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhou
authors.affiliation: c School of Chemistry and Chemical Engineering, Shandong University , Jinan , P.R. China.
authors.forename: Qingxin
authors.initials: Q
authors.lastname: Mu
authors.affiliation: c School of Chemistry and Chemical Engineering, Shandong University , Jinan , P.R. China.
authors.forename: Gaoxing
authors.initials: G
authors.lastname: Su
authors.affiliation: c School of Chemistry and Chemical Engineering, Shandong University , Jinan , P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.affiliation: b Laboratory for Molecular Modeling , Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina , Chapel Hill , NC , USA , and.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tropsha
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D062067:Chemical Safety; D003198:Computer Simulation; D017076:Computer-Aided Design; D016208:Databases, Factual; D037742:Nanotubes, Carbon / Q000009:adverse effects / Q000737:chemistry* / Q000633:toxicity*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship
chemical_list: D037742:Nanotubes, Carbon
keywords: Carbon nanotubes; QSAR; cheminformatics; nanotoxicity; virtual screening