Kim, Taewoo Zhen, Juyuan Lee, Junghyun Bauer, Robert Lee, Changkeun Kwon, Bong-Oh Chae, Keun Hwa Hong, Seongjin Giesy, John P. Chang, Gap Soo Khim, Jong Seong 2024-01-19T17:02:19Z 2024-01-19T17:02:19Z 2021-09-02 2020-08 2045-2322 https://pubs.kist.re.kr/handle/201004/118332 Understanding what and how physico-chemical factors of a ligand configure conditions for ligand-receptor binding is a key to accurate assessment of toxic potencies of environmental pollutants. We investigated influences of the dipole-driven orientation and resulting directional configuration of ligands on receptor binding activities. Using physico-chemical properties calculated by ab initio density functional theory, directional reactivity factors (DRF) were devised as main indicators of toxic potencies, linking molecular ligand-receptor binding to in vitro responses. The directional reactive model was applied to predict variation of aryl hydrocarbon receptor-mediated toxic potencies among homologues of chrysene with structural modifications such as the numbers of constituent benzene rings, methylation and hydroxylation. Results of predictive models were consistent with empirical potencies determined by use of the H4IIE-luc transactivation bioassay. The experiment-free approach based on first principles provides an analytical framework for estimating molecular bioactivity in silico and complements conventional empirical approaches to studying molecular initiating events in adverse outcome pathways. English Nature Publishing Group Influence of ligand's directional configuration, chrysenes as model compounds, on the binding activity with aryl hydrocarbon receptor Article 10.1038/s41598-020-70704-9 1 Scientific Reports, v.10, no.1 Scientific Reports 10 1 Y scie scopus 000573282100013 2-s2.0-85089434435 Multidisciplinary Sciences Science & Technology - Other Topics Article QSAR MODELS FREE-ENERGIES IN-VIVO TOXICITY DOCKING RECOGNITION CHEMICALS BIOASSAYS PATHWAYS STATES physico-chemical factors of a ligand configure ligandreceptor dipole-driven orientation directional reactivity factors ab initio density functional theory first principles