Journal:JBSD:38

<big>I-Chi Hung, Su-sen Chang, Pei-Chun, Chang, Cheng-Chun Lee, Calvin Yu-Chian Chen</big> <ref>doi 10.1080/07391102.2012.741052</ref>

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]], <font color='darkmagenta'><b>colored in darkmagenta</b></font>) 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'', <span style="color:lime;background-color:black;font-weight:bold;">colored in green</span>), <scene name='Journal:JBSD:38/Cv/4'>(+)-N-methyllaurotetanine</scene> (origin: ''Lindera aggregate'', <span style="color:deeppink;background-color:black;font-weight:bold;">colored in deeppink</span>), and <scene name='Journal:JBSD:38/Cv/5'>(+)-1(R)-Coclaurine</scene> (origin: ''Nelumbonucifera Gaertn'', <span style="color:salmon;background-color:black;font-weight:bold;">colored in salmon</span>) 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 <scene name='Journal:JBSD:38/Cv/11'>(+)-1(R)-Coclaurine</scene> was stabilized by <scene name='Journal:JBSD:38/Cv/12'>Leu975 and Gly1055</scene> (<span style="color:yellow;background-color:black;font-weight:bold;">key residues are colored in yellow</span>). 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.