Biology subjects

Oliveira, A. B.

Publications and source records attributed to Oliveira, A. B..

3 recordsLinked to original sources

bioRxiv2026

The compartmental polarization of interphase human chromosomes within the nucleus: A mechanism for transcriptional regulation of large chromosomes

The structure and dynamics of individual chromosomes are significantly modulated by their local environment within the nucleus. It has long been established that heterochromatin (B compartment loci) associates with the lamina meshwork that lines the inner nuclear envelope. However, the extent to which these interactions perturb the chromosomal organization within a territory remains unclear. Using computer simulations and published imaging data, we further characterize the interaction between chromatin and the lamina and find striking consequences of lamina-association on the chromosomal structural ensemble. We find that lamina-associating chromosomes have their compartmentalization polarized in a direction perpendicular to the nuclear surface. Further, lamina-associated chromosomes exhibit shorter average distances between euchromatin loci (A compartment) than chromosomes without lamina contact. Energy landscape analysis of our simulations reveal that the sequestration of heterochromatin to the lamina allows for euchromatin to form more spatial contacts with other segments of euchromatin. The compaction of euchromatin due to lamina-association also diminishes the mobility of these regions. These findings suggest a mechanism for bringing together euchromatic segments that are separated by large genomic distances within a chromosome, potentially to share transcriptional machinery and enhance transcription for large chromosomes, which are often found at the nuclear periphery.

biophysics↗

bioRxiv2024

Compaction-mediated segregation of partly replicated bacterial chromosome

Faithful chromosome segregation during bacterial replication requires global reorganization of the nucleoid, where Structural Maintenance of Chromosomes (SMC) complexes play a crucial role. Here we develop an energy-landscape framework that integrates data-driven pairwise interactions with coarse-grained polymer physics to infer the 3D architectural ensembles of Escherichia coli and Bacillus subtilis chromosomes throughout replication. We show that SMC-mediated long-range lengthwise compaction reshapes the nucleoid to induce a robust mid-replication transition in which the terminus relocates toward the nucleoid center and duplicated origins segregate toward opposite cell halves. SMC-deficient mutants lack this transition and instead exhibit emergent nematic-like alignment of sister chromosomes that impedes segregation. A distinctive inter-sister Hi-C signature accompanies the emergence of the nematic alignment. By systematically tuning nonspecific inter-sister adhesion, we reveal that SMC activity expands the physical regime permitting faithful segregation. This buffering protects segregation against adhesive forces intrinsic to the crowded bacterial nucleoid. Our framework provides mechanistic insight into SMC-dependent co-replication segregation across bacterial species, yielding experimentally testable predictions for imaging and sister-chromosome-resolved Hi-C.

biophysics↗

bioRxiv2021

SMOG 2 and OpenSMOG: Extending the limits of structure-based models

Applying simulations with structure-based (G[o]-like) models has proven to be an effective strategy for investigating the factors that control biomolecular dynamics. The common element of these models is that some (or all) of the intra/inter-molecular inter-actions are explicitly defined to stabilize an experimentally-determined structure. To facilitate the development and application of this broad class of models, we previously released the SMOG 2 software package. This suite allows one to easily customize and distribute structure-based (i.e. SMOG) models for any type of polymer-ligand system. Since its original release, user feedback has driven the implementation of numerous enhancements. Here, we describe recent extensions to the software and demonstrate the capabilities of the most recent version, SMOG v2.4. Changes include new tools that aid user-defined customization of force fields, as well as an interface with the OpenMM simulation libraries (OpenSMOG v1.0). To illustrate the utility of these advances, we present several applications of SMOG2 and OpenSMOG, which include systems with millions of atoms, long polymers and explicit ions. We also highlight how one can incorporate non-structure-based (e.g. AMBER-based) energetics to define a hybrid class of models. The representative applications include large-scale rearrangements of the SARS-CoV-2 Spike protein, the HIV-1 capsid in the presence of explicit ions, and crystallographic lattices of ribosomes and proteins. In summary, SMOG 2 and OpenSMOG provide robust support for researchers who seek to apply structure-based models to large and/or intricate biomolecular systems.

biophysics↗