Predicting protein functional motions: an old recipe with a new twist

Abstract : Large macromolecules, including proteins and their complexes, very often adopt multiple conformations. Some of them can be seen experimentally, for example with X-ray crystallography or cryo-electron microscopy. This structural heterogeneity is not occasional and is frequently linked with specific biological function. Thus, the accurate description of macromolecular conformational transitions is crucial for understanding fundamental mechanisms of life's machinery. We report on a real-time method to predict such transitions by extrapolating from instantaneous eigen-motions, computed using the normal mode analysis, to a series of twists. We demonstrate the applicability of our approach to the prediction of a wide range of motions, including large collective opening-closing transitions and conformational changes induced by partner binding. We also highlight particularly difficult cases of very small transitions between crystal and solution structures. Our method guaranties preservation of the protein structure during the transition and allows to access conformations that are unreachable with classical normal mode analysis. We provide practical solutions to describe localized motions with a few low-frequency modes and to relax some geometrical constraints along the predicted transitions. This work opens the way to the systematic description of protein motions, whatever their degree of collectivity. Our method is available as a part of the NOn-Linear rigid Block (NOLB) package at https://team.inria.fr/nano-d/software/ nolb-normal-modes/.
Document type :
Preprints, Working Papers, ...
Complete list of metadatas

Cited literature [83 references]  Display  Hide  Download

https://hal.archives-ouvertes.fr/hal-02291552
Contributor : Sergei Grudinin <>
Submitted on : Thursday, September 19, 2019 - 4:36:59 AM
Last modification on : Tuesday, October 15, 2019 - 1:29:37 AM

File

Manuscript.pdf
Files produced by the author(s)

Identifiers

Citation

Sergei Grudinin, Elodie Laine, Alexandre Hoffmann. Predicting protein functional motions: an old recipe with a new twist. 2019. ⟨hal-02291552⟩

Share

Metrics

Record views

49

Files downloads

105