Determination of the Structure and Dynamics of the Fuzzy Coat of an Amyloid Fibril of IAPP Using Cryo-Electron Microscopy.

ABSTRACT: In recent years, major advances in cryo-electron microscopy (cryo-EM) have enabled the routine determination of complex biomolecular structures at atomistic resolution. An open challenge for this approach, however, concerns large systems that exhibit continuous dynamics. To address this problem, we developed the metadynamic electron microscopy metainference (MEMMI) method, which incorporates metadynamics, an enhanced conformational sampling approach, into the metainference method of integrative structural biology. MEMMI enables the simultaneous determination of the structure and dynamics of large heterogeneous systems by combining cryo-EM density maps with prior information through molecular dynamics, while at the same time modeling the different sources of error. To illustrate the method,

SUBMITTER: Faidon Brotzakis Z 

PROVIDER: S-EPMC10433526 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature