Activating mutations in the kinase domain of anaplastic lymphoma kinase (ALK) have been implicated in the early childhood cancer, neuroblastoma.Using molecular dynamics based methods, we investigate how these point mutations promote constitutive kinase activation in neuroblastoma patients.  We demonstrate that these mutations may disrupt key hydrophobic and hydrophilic networks which stabilize the inactive conformation of the kinase domain, and we compare our results to studies on the ErbB family of receptor tyrosine kinases.

Understanding kinase activation of ALK in neuroblastoma patients

244th National Meeting (2012)

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