Dynamics fingerprints of active conformers of epidermal growth factor receptor kinase.

摘要: Epidermal growth factor receptor (EGFR) is a prototypical cell-surface that plays key role in the regulation of cellular signaling, proliferation and differentiation. Mutations its kinase domain have been associated with development variety cancers and, therefore, it has target drug design. Single amino acid substitutions (SASs) this proven to alter equilibrium pre-existing conformer populations. Despite advances structural descriptions so-called active inactive conformations, dynamics aspects characterize them not thoroughly studied yet. As dynamic behaviors molecular motions proteins are important for complete understanding their structure-function relationships we present novel procedure, using (or based on) normal mode analysis, identify collective shared among different conformers EGFR kinase. The method allows comparison patterns low-frequency vibrational modes defining representative directions motions. Our procedure able emphasize main similarities differences between conformers. In case kinase, two found as fingerprints Protein motion along both reveals significant impact on cavity volume pocket site. Otherwise, exhibit more heterogeneous distribution © 2018 Wiley Periodicals, Inc.