Computational IR Spectroscopy of Insulin Dimer Structure and Conformational Heterogeneity.

ABSTRACT: We have investigated the structure and conformational dynamics of insulin dimer using a Markov state model (MSM) built from extensive unbiased atomistic molecular dynamics simulations and performed infrared spectral simulations of the insulin MSM to describe how structural variation within the dimer can be experimentally resolved. Our model reveals two significant conformations to the dimer: a dominant native state consistent with other experimental structures of the dimer and a twisted state with a structure that appears to reflect a ∼55° clockwise rotation of the native dimer interface. The twisted state primarily influences the contacts involving the C-terminus of insulin's B chain, shifting the registry of its intermolecular hydrogen bonds and reorganizing its side-chain packing. The M

SUBMITTER: Feng CJ 

PROVIDER: S-EPMC8442834 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature