Unveiling functional motions based on point mutations in biased signaling systems: A normal mode study on Nerve Growth Factor bound to TrkA

摘要: Many receptors elicit signal transduction by activating multiple intracellular pathways. This may be triggered a nonspecific ligand, which simultaneously activates all receptor’s signaling paths. In addition, the binding of biased ligand preferentially elicits one path over another, in process called signaling. Identifying functional motions related to each these distinct pathways have direct impact development new efficient and specific drugs. Here we show how detect considering case NGF/TrkA-Ig2 complex. TrkA activation mediated NGF depends on structural that trigger neuronal growth, survival nervous system. R221W mutation ngf gene impairs nociceptive wide spread effects this complex, leading deletion collective important Our results suggest subtle changes interaction network within neurotrophic factors due point are sufficient inhibit necessary conformational for activation. The methodological approach presented article based conjunctively normal mode analysis experimentally observed alterations mutations provides an essential tool unveiling disease, turn could drug design study.