Journal:JBSD:38

Cognitive impairment is an emerging issue and increasing research points to the significant role of insulin-like growth factor I (IGF-I) in cognitive brain functions. <scene name='Journal:JBSD:38/Cv/3'>IGF receptor </scene> (IGF-IR, PDB ID: [[3i81]]) activation is critical for IGF-I to elicit desirable cognitive functions. Traditional Chinese medicine (TCM) ligands <scene name='Journal:JBSD:38/Cv/2'>3-(2-carboxyphenyl)-4(3H)-quinazolinone</scene> (orgin: ''Isatisin digotica''), <scene name='Journal:JBSD:38/Cv/4'>(+)-N-methyllaurotetanine</scene> (origin: ''Lindera aggregate''), and <scene name='Journal:JBSD:38/Cv/5'>(+)-1(R)-Coclaurine</scene> (origin: ''Nelumbonucifera Gaertn'') showed high binding affinity towards IGF-IR at the binding site defined by the control in PDB ID: [[3i81]]. Molecular dynamics simulation revealed that the TCM ligands were secured at the opening of the IGF-IR binding site for the duration of the MD. <scene name='Journal:JBSD:38/Cv/7'>3-(2-carboxyphenyl)-4(3H)-quinazolinone</scene> was stabilized by <scene name='Journal:JBSD:38/Cv/8'>Asp1056</scene>, <scene name='Journal:JBSD:38/Cv/9'>(+)-N-methyllaurotetanine</scene> was stabilized by <scene name='Journal:JBSD:38/Cv/10'>Leu975 and Asp1056</scene>, and (+)-1(R)-Coclaurine was stabilized by Leu975 and Gly1055 (global view file: top3_971top.pdb, top3_971top.png; local zoomed in file: top3_971topzoomin.pdb; top3_971topzoomin.png). Four different quantitative-structure activity relationship models consistently predicted bioactivity of the TCM ligands towards IGF-IR. In summary, the TCM candidates exhibit drug-like potential in both structural-based and ligand-based properties and may have potential for further applications in enhancing cognition.