About

Vinícius Contessoto is an Assistant Research Professor in the Department of Physics and Astronomy at Rice University. His research focuses on developing models to explore chromatin dynamics and function, with an interest in understanding how the genome is organized across different organisms and how chromosomes change shapes during various stages of the cell cycle. Additionally, he investigates protein folding and engineering, aiming to develop methods to predict epitopes for immunization strategies and to predict mutations that can increase enzyme thermostability.

Research topics

• Computer Security
• Computer Science
• Biology
• Medicine
• Genetics
• Virology
• Evolutionary biology
• Immunology
• Computational biology

Selected publications

• Exploring the energy landscape of bacterial chromosome segregation

  Proceedings of the National Academy of Sciences · 2026-03-17 · 1 citations

  articleOpen access

  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 intersister Hi-C signature accompanies the emergence of the nematic alignment. By systematically tuning nonspecific intersister 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 coreplication segregation across bacterial species, yielding experimentally testable predictions for imaging and sister-chromosome-resolved Hi-C.

  PublisherDOI

• Energy landscape analysis of the development of the chromosome structure across the cell cycle

  Proceedings of the National Academy of Sciences · 2025-03-20 · 5 citations

  articleOpen access1st authorCorresponding

  During mitosis, there are significant structural changes in chromosomes. We used a maximum entropy approach to invert experimental Hi-C data to generate effective energy landscapes for chromosomal structures at different stages during the cell cycle. Modeled mitotic structures show a hierarchical organization of helices of helices. High-periodicity loops span hundreds of kilobases or less, while the other low-periodicity ones are larger in genomic separation, spanning several megabases. The structural ensembles reveal a progressive decrease in compartmentalization from interphase to mitosis, accompanied by the appearance of a second diagonal in prometaphase, indicating an organized array of loops. While there is a local tendency to form chiral helices, overall, no preferential left-handed or right-handed chirality appears to develop on the time scale of the cell cycle. Chromatin thus appears to be a liquid crystal containing numerous defects that anneal rather slowly.

  PublisherDOI

• Mapping the energy landscape of a fold‐switching protein <scp>MAD2</scp>

  Protein Science · 2025-10-11 · 1 citations

  articleCorresponding

  The mitotic arrest deficiency 2 (MAD2) exists in inactive and active forms under physiologic conditions. In its active conformation, MAD2 binds to the cell division cycle protein 20 (Cdc20) and prevents the separation of duplicated chromosomes. In the inactive conformation, the C-terminal region of MAD2 covers the binding motif for the Cdc20 target. Here, we investigated the MAD2 activation mechanism using structure-based models (SBMs) simulations, amino acid coevolution, and structural frustration analysis. MAD2 switches between active and inactive conformations while maintaining core stability. Simulations reveal an intermediate state during the transition consistent with recent time-resolved NMR experiments. Coevolution analysis captures native contacts for both states. These native contacts, present in both conformations, compete, driving transitions between different protein states. This competition leads to a frustrated energy landscape. Frustration analysis further shows that highly frustrated residues are present in both conformations, particularly in the fold-switching segments.

  PublisherDOI

• Energy landscapes in protein folding

  Elsevier eBooks · 2025-01-01

  book-chapter1st authorCorresponding
  PublisherDOI

• Epigenetics is all you need: A transformer to decode chromatin structural compartments from the epigenome

  PLoS Computational Biology · 2025-12-03 · 1 citations

  articleOpen accessCorresponding

  Chromatin within the nucleus adopts complex three-dimensional structures that are crucial for gene regulation and cellular function. Recent studies have revealed the presence of distinct chromatin subcompartments beyond the traditional A/B compartments (eu- and hetero-chromatin), each exhibiting unique structural and functional properties. Here, we introduce TECSAS (Transformer of Epigenetics to Chromatin Structural AnnotationS), a deep learning model based on the Transformer architecture, designed to predict chromatin subcompartment annotations directly from epigenomic data. TECSAS leverages information from histone modifications, transcription factor binding profiles, and RNA-Seq data to decode the relationship between the biochemical composition of chromatin and its 3D structural behavior. TECSAS achieves high accuracy in predicting subcompartment annotations and reveals the influence of long-range epigenomic context on chromatin organization. Furthermore, we demonstrate the model's capability to predict the association of loci with nuclear bodies, such as the lamina, nucleoli, and speckles, providing insights into the role of these structures in shaping the 3D genome organization. This study highlights the potential of deep learning models for deciphering the complex interplay between epigenomic features and 3D genome organization, allowing us to better understand genome structure and function.

  PublisherDOI

• Sequence-based calculation of local energetic frustration in proteins

  Structural Dynamics · 2025-11-01

  articleOpen access

  Given proteins' fundamental importance in human health and catalysis, the relationships between protein sequence, structure, dynamics, and function have become a topic of great interest. One way to extract information from proteins is to compute the local energetic frustration of their native state. Traditionally, energetic frustration calculations require protein structures as a starting point. However, using a single protein structure to evaluate the energetic frustration for a given amino acid sequence does not always fully represent the protein's structural ensemble. Therefore, we have developed a sequence-based method to evaluate energetic frustration in proteins using direct coupling analysis and statistical potentials. Our approach exhibits significant agreement with established structure-based frustration methods in terms of their mutual agreement with crystallographic B-factor. Moreover, our sequence-based method shows elevated precision in classifying high B-factor residues, suggesting that it has some robustness to unstructured regions of proteins.

  PublisherOA PDFDOI

• The synergy between compartmentalization and motorization in chromatin architecture

  The Journal of Chemical Physics · 2025-03-19 · 3 citations

  article

  High-resolution techniques capable of manipulating from single molecules to millions of cells are combined with three-dimensional modeling followed by simulation to comprehend the specific aspects of chromosomes. From the theoretical perspective, the energy landscape theory from protein folding inspired the development of the minimal chromatin model (MiChroM). In this work, two biologically relevant MiChroM energy terms were minimized under different conditions, revealing a competition between loci compartmentalization and motor-driven activity mechanisms in chromatin folding. Enhancing the motor activity energy baseline increased the lengthwise compaction and reduced the polymer entanglement. Concomitantly, decreasing compartmentalization-related interactions reduced the overall polymer collapse, although compartmentalization given by the microphase separation remained almost intact. For multiple chromosome simulations, increased motorization intensified the territory formation of the different chains and reduced compartmentalization strength lowered the probability of contact formation of different loci between multiple chains, approximating to the experimental inter-contacts of the human chromosomes. These findings have direct implications for experimental data-driven chromosome modeling, specially those involving multiple chromosomes. The interplay between phase-separation and territory formation mechanisms should be properly implemented in order to recover the genome architecture and dynamics, features that might play critical roles in regulating nuclear functions.

  PublisherDOI

• Exploring the energy landscape of bacterial chromosome segregation

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-07-28 · 2 citations

  preprintOpen access

  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.

  PublisherOA PDFDOI

• Investigating human chromosome organization by whole-genome simulations

  Biophysical Journal · 2024-02-01

  articleOpen access
  PublisherOA PDFDOI

• Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample

  Cell · 2024-07-01 · 31 citations

  articleOpen access

  Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (†Mammuthus primigenius) that died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding 28 chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, and inactive X chromosome (Xi) superdomains persist. The active and inactive genome compartments in mammoth skin more closely resemble Asian elephant skin than other elephant tissues. Our analyses uncover new biology. Differences in compartmentalization reveal genes whose transcription was potentially altered in mammoths vs. elephants. Mammoth Xi has a tetradic architecture, not bipartite like human and mouse. We hypothesize that, shortly after this mammoth's death, the sample spontaneously freeze-dried in the Siberian cold, leading to a glass transition that preserved subfossils of ancient chromosomes at nanometer scale.

  PublisherOA PDFDOI

Frequent coauthors

• José N. Onuchic

  Rice University

  169 shared

• E Aiden

  Broad Institute

  80 shared

• Michele Di Pierro

  Northeastern University

  78 shared

• Esteban Dodero‐Rojas

  77 shared

• Antonio B. Oliveira

  Rice University

  61 shared

• S.K. Burley

  Rutgers, The State University of New Jersey

  47 shared

• Peter G. Wolynes

  Rice University

  44 shared

• Matheus F. Mello

  Rice University

  44 shared