Molecular Modeling of ALK L1198F and/or G1202R Mutations to Determine Differential Crizotinib Sensitivity.

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that has been recognized as a therapeutic target for EML4-ALK fusion-positive nonsmall cell lung cancer (NSCLC) treatment using type I kinase inhibitors such as crizotinib to take over the ATP binding site. According to Shaw's measurements, ALK carrying G1202R mutation shows reduced response to crizotinib (IC = 382 nM vs. IC = 20 nM for wild-type), whereas L1198F mutant is more responsive (IC = 0.

Molecular Modeling for Structural Insights Concerning the Activation Mechanisms of F1174L and R1275Q Mutations on Anaplastic Lymphoma Kinase.

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase involved in various cancers. In its basal state, the structure of ALK is in an autoinhibitory form stabilized by its A-loop, which runs from the N-lobe to the C-lobe of the kinase. Specifically, the A-loop adopts an inhibitory pose with its proximal A-loop helix (αAL-helix) to anchor the αC-helix orientation in an inactive form in the N-lobe; the distal portion of the A-loop is packed against the C-lobe to block the peptide substrate from binding.

Correction: Surface modification of carbon cloth anodes for microbial fuel cells using atmospheric-pressure plasma jet processed reduced graphene oxides.

[This corrects the article DOI: 10.1039/C7RA11914C.].

Molecular modeling on HIF-2α-ARNT dimer destabilization caused by R171A and/or V192D mutations in HIF-2α.

Oxygen homeostasis in normal and tumor cells is mediated by hypoxia-inducible factors (HIFs), which are active as heterodimer complexes, such as HIF-2α-aryl hydrocarbon receptor nuclear translocator (ARNT) and HIF-1α-ARNT. A series of mutations on the interfaces between HIF-2α and ARNT and on the domain-domain interface within HIF-2α has been reported to exert varying effects on HIF-2α-ARNT dimerization. In the present study, molecular dynamic simulations were conducted to evaluate HIF-2α mutations, namely R171A, V192D, and R171A/V192D, which are not involved in the interaction with ARNT but impede HIF-2α-ARNT dimerization.