Biophysics, Structural Biology, Drug Discovery, Multidisciplinary
5
Scopus Publications
25
Scholar Citations
4
Scholar h-index
1
Scholar i10-index
Scopus Publications
Impact of Structural Relaxation on Protein–Protein Docking in Large Macromolecular Complexes Raissa Santos de Lima Rosa, Ana Carolina Silva Bulla, Rafael C. Bernardi, Manuela Leal da Silva Applied Biosciences, 2025 Protein–protein docking is a cornerstone of computational structural biology, yet its reliability for large, multimeric assemblies remains uncertain. Standard workflows typically include geometry optimization or molecular dynamics equilibration to relieve local strains and improve input quality, but the extent to which these preparatory steps alter docking outcomes has not been systematically evaluated. Here, we address this question using the mitochondrial chaperonin Hsp60, a dynamic double-ring complex essential for protein folding, and MIX, a kinetoplastid-specific protein with unresolved function, as a stress test system. By comparing docking predictions across minimized, equilibrated, and ensemble-refined structures of Hsp60 in three conformational states (apo, ATP-bound, and ATP–Hsp10), we show that structural relaxation profoundly reshapes the docking landscape. Minimization alone often yielded favorable scores but localized binding, while longer MD trajectories exposed alternative sites, including central cavity, equatorial ATP pocket, and apical domain, each consistent with distinct regulatory hypotheses. These findings reveal that docking outcomes are highly sensitive to receptor preparation, especially in complexes undergoing large conformational transitions. More broadly, our study highlights an underappreciated vulnerability of docking pipelines and calls for ensemble-based and dynamics-aware approaches when predicting interactions in large biomolecular machines.
Bacterial efflux pump OMPs as vaccine candidates against multidrug-resistant Gram-negative bacteria Thaynara O Silva, Ana Carolina S Bulla, Bárbara A Teixeira, Vinnicius Machado Schelk Gomes, Thiago Raposo, et al. Journal of Leukocyte Biology, 2024 The emergence and propagation of bacteria resistant to antimicrobial drugs is a serious public health threat worldwide. The current antibacterial arsenal is becoming obsolete, and the pace of drug development is decreasing, highlighting the importance of investment in alternative approaches to treat or prevent infections caused by antimicrobial-resistant bacteria. A significant mechanism of antimicrobial resistance employed by Gram-negative bacteria is the overexpression of efflux pumps that can extrude several compounds from the bacteria, including antimicrobials. The overexpression of efflux pump proteins has been detected in several multidrug-resistant Gram-negative bacteria, drawing attention to these proteins as potential targets against these pathogens. This review will focus on the role of outer membrane proteins from efflux pumps as potential vaccine candidates against clinically relevant multidrug-resistant Gram-negative bacteria, discussing advantages and pitfalls. Additionally, we will explore the relevance of efflux pump outer membrane protein diversity and the possible impact of vaccination on microbiota.
The Escherichia coli TolC efflux pump protein is immunogenic and elicits protective antibodies Thaynara O Silva, Bárbara A Teixeira, Leon V S Costa, Luiza S Barbosa, Lucas C do Nascimento, et al. Journal of Leukocyte Biology, 2024 Antimicrobial resistance is an increasing worldwide public health burden that threatens to make existent antimicrobials obsolete. An important mechanism of antimicrobial resistance is the overexpression of efflux pumps, which reduce the intracellular concentration of antimicrobials. TolC is the outer membrane protein of an efflux pump that has gained attention as a therapeutic target. Little is known about the immune response against TolC. Here, we evaluated the immune response against TolC from Escherichia coli. TolC in silico epitope prediction showed several residues that could bind to human antibodies, and we showed that human plasma presented higher titers of anti-TolC IgG and IgA, than IgM. E. coli recombinant TolC protein stimulated macrophages in vitro to produce nitric oxide, as well as interleukin-6 and tumor necrosis factor α, assessed by Griess assay and enzyme-linked immunosorbent assay, respectively. Immunization of mice with TolC intraperitoneally and an in vitro restimulation led to increased T cell proliferation and interferon γ production, evaluated by flow cytometry and enzyme-linked immunosorbent assay, respectively. TolC mouse immunization stimulated anti-TolC IgM and IgG production, with higher levels of IgG1 and IgG2, among the IgG subclasses. Anti-TolC murine antibodies could bind to live E. coli and increase bacterial uptake and elimination by macrophages in vitro. Intraperitoneal or intranasal, but not oral, immunizations with inactivated E. coli also led to anti-TolC antibody production. Finally, TolC immunization increased mouse survival rates to antimicrobial-sensitive or resistant E. coli infection. Our results showed that TolC is immunogenic, leading to the production of protective antibodies against E. coli, reinforcing its value as a therapeutic target.
RECENT SCHOLAR PUBLICATIONS
Impact of Structural Relaxation on Protein–Protein Docking in Large Macromolecular Complexes RSL Rosa, ACS Bulla, RC Bernardi, M Leal da Silva Applied Biosciences 4 (4), 48 , 2025 2025 Citations: 2
Computational Methods in Immunoinformatics: Epitope Discovery and Diagnostic Applications ACS Bulla, A Sbano da Silva, B Prado Sereno, MFR Dias, M Leal da Silva ACS omega 10 (39), 44816-44839 , 2025 2025 Citations: 5
RND/HAE-1 members in the Pseudomonadota phylum: Exploring multidrug resistance VMS Gomes, ACS Bulla, PHM Torres, M Leal da Silva Biophysical Reviews 17 (2), 687-699 , 2025 2025 Citations: 4
BIOINFO #04 - Revista Brasileira de Bioinformática e Biologia Computacional AL da Silva, A de Paula Dias da Silva, ACS Bulla, AR Gonçalves, ... https://bioinfo.com.br/bioinfo-04/ 4 , 2024 2024
Bacterial efflux pump OMPs as vaccine candidates against multidrug-resistant Gram-negative bacteria TO Silva, ACS Bulla, BA Teixeira, VMS Gomes, T Raposo, LS Barbosa, ... Journal of Leukocyte Biology 116 (6), 1237-1253 , 2024 2024 Citations: 10
The Escherichia coli TolC efflux pump protein is immunogenic and elicits protective antibodies TO Silva, BA Teixeira, LVS Costa, LS Barbosa, LC do Nascimento, ... Journal of Leukocyte Biology 116 (6), 1398-1411 , 2024 2024 Citations: 4
BIOINFO #03 - Revista Brasileira de Bioinformática e Biologia Computacional D Mariano, A de Paula Dias da Silva, AS Cremonesi, ACS Bulla, ... https://bioinfo.com.br/bioinfo-03/ 3 , 2023 2023
BIOINFO# 02-Revista Brasileira de Bioinformática e Biologia Computacional LL Bastos, AA Puelles, V Paixão, E Utsch, WG Nogueira, TS Bialves, ... Alfahelix Publicações , 2022 2022
De olho na covid-19 https://nupem.ufrj.br/de-olho-na-covid-19-3/ 3 , 2021 2021
Experiências de divulgação científica e letramento científico sobre moléculas durante a pandemia da Covid-19 ML da Silva, AAP Junior, EG Ribeiro, LF Fonseca, ACS Bulla, MFR Dias Raízes e rumos 8 (2), 252-263 , 2020 2020
De olho na COVID-19 https://nupem.ufrj.br/de-olho-na-covid-19-volume-2/ 2 , 2020 2020
MOST CITED SCHOLAR PUBLICATIONS
Bacterial efflux pump OMPs as vaccine candidates against multidrug-resistant Gram-negative bacteria TO Silva, ACS Bulla, BA Teixeira, VMS Gomes, T Raposo, LS Barbosa, ... Journal of Leukocyte Biology 116 (6), 1237-1253 , 2024 2024 Citations: 10
Computational Methods in Immunoinformatics: Epitope Discovery and Diagnostic Applications ACS Bulla, A Sbano da Silva, B Prado Sereno, MFR Dias, M Leal da Silva ACS omega 10 (39), 44816-44839 , 2025 2025 Citations: 5
RND/HAE-1 members in the Pseudomonadota phylum: Exploring multidrug resistance VMS Gomes, ACS Bulla, PHM Torres, M Leal da Silva Biophysical Reviews 17 (2), 687-699 , 2025 2025 Citations: 4
The Escherichia coli TolC efflux pump protein is immunogenic and elicits protective antibodies TO Silva, BA Teixeira, LVS Costa, LS Barbosa, LC do Nascimento, ... Journal of Leukocyte Biology 116 (6), 1398-1411 , 2024 2024 Citations: 4
Impact of Structural Relaxation on Protein–Protein Docking in Large Macromolecular Complexes RSL Rosa, ACS Bulla, RC Bernardi, M Leal da Silva Applied Biosciences 4 (4), 48 , 2025 2025 Citations: 2
BIOINFO #04 - Revista Brasileira de Bioinformática e Biologia Computacional AL da Silva, A de Paula Dias da Silva, ACS Bulla, AR Gonçalves, ... https://bioinfo.com.br/bioinfo-04/ 4 , 2024 2024
BIOINFO #03 - Revista Brasileira de Bioinformática e Biologia Computacional D Mariano, A de Paula Dias da Silva, AS Cremonesi, ACS Bulla, ... https://bioinfo.com.br/bioinfo-03/ 3 , 2023 2023
BIOINFO# 02-Revista Brasileira de Bioinformática e Biologia Computacional LL Bastos, AA Puelles, V Paixão, E Utsch, WG Nogueira, TS Bialves, ... Alfahelix Publicações , 2022 2022
De olho na covid-19 https://nupem.ufrj.br/de-olho-na-covid-19-3/ 3 , 2021 2021
Experiências de divulgação científica e letramento científico sobre moléculas durante a pandemia da Covid-19 ML da Silva, AAP Junior, EG Ribeiro, LF Fonseca, ACS Bulla, MFR Dias Raízes e rumos 8 (2), 252-263 , 2020 2020
De olho na COVID-19 https://nupem.ufrj.br/de-olho-na-covid-19-volume-2/ 2 , 2020 2020
