Biology subjects

Sabei, A.

Publications and source records attributed to Sabei, A..

3 recordsLinked to original sources

bioRxiv2026

Mechanical response of the RecA nucleoprotein filament to increasing D-loop length

AO_SCPLOWBSTRACTC_SCPLOWProtein filaments play fundamental functions in the cell, ranging from scaffolding like in the cytoskeleton to sensing and transmitting forces and torques. Here we address the case of the nucleoprotein filaments (NPFs) of homologous recombination (HR) formed by the polymerization of the RecA protein on DNA. In contrast to the cytoskeleton filaments, the HR filaments are not known to exert or sense forces. However the stress in the stretched and unwound DNA bound to those filaments was shown to play a role in promoting DNA strand exchange during the early stage of the HR mechanism. Here we use molecular dynamics simulations to examine whether the strain in the nucleoprotein filament upon strand exchange progression and D-loop formation may influence subsequent steps of the HR process. Our results indicate that the filament mechanical properties are sensitive to the length of DNA incorporated in the D-loop. The response we observe upon increasing the D-loop length is first elastic, up to a threshold that we estimate to be 27 incorporated base pairs, after which the NPF enters a new stage where the protein-DNA connectivities are reorganized. Notably, the DNA displaced strand locally switches from site II to site III, a newly characterized binding site. We discuss the possible consequence of this mechanical response of the NPFs for the course of the HR process.

molecular biology↗

bioRxiv2023

The dynamics of protein-RNA interfaces using all-atom molecular dynamics simulations

Facing the current challenges raised by human health diseases requires the understanding of cell machinery at a molecular level. The interplay between proteins and RNA is key for any physiological phenomenon, as well protein-RNA interactions. To understand these interactions many experimental techniques have been developed, spanning a very wide range of spatial and temporal resolutions. In particular, the knowledge of tridimensional structures of protein-RNA complexes provides structural, mechanical and dynamical pieces of information essential to understand their functions. To get insights into the dynamics of protein-RNA complexes, we carried out all-atom molecular dynamics simulations in explicit solvent on nine different protein-RNA complexes with different functions and interface size by taking into account the bound and unbound forms. First, we characterized structural changes upon binding and for the RNA part the change in the puckering. Second, we extensively analyzed the in-terfaces, their dynamics and structural properties, and the structural waters involved in the binding, as well as the contacts mediated by them. Based on our analysis, the interfaces rearranged during the simulation time showing alternative and stable residue-residue contacts with respect to the experimental structure.

biochemistry↗

bioRxiv2022

Internal Normal Mode Analysis applied to RNA flexibility and conformational changes

We investigated the capability of internal normal modes to reproduce RNA dynamics and predict observed RNA conformational changes, and, notably, those induced by the formation of RNA-protein and RNA-ligand complexes. Here, we extended our iNMA approach developed for proteins to study RNA molecules using a simplified representation of RNA structure and its potential energy. Three datasets were also created to investigate different aspects. Despite all the approximations, our study shows that iNMA is a suitable method to take into account RNA flexibility and describe its conformational changes opening the route to its applicability in any integrative approach where these properties are crucial.

biophysics↗