A. Sofia F. Oliveira

Senior Research Fellow @ University of Bristol

email: sofia.oliveira@bristol.ac.uk

Present Research Interests

The research in my group explores the principles that govern the dynamics of biological molecules to understand how sequence variations shape function. By combining advanced computational methods with experimental data, our work uncovers mechanisms of biomolecular function and disease, guiding the design of systems for biomedical and biotechnological applications.

Our research explores a diverse range of biomolecular systems, including soluble enzymes, nucleic acids, and membrane proteins. We focus on targets such as nicotinic acetylcholine receptors and other Cys-loop family members, cytochrome c oxidase, ATP-binding cassette (ABC) transporters, and enzymes implicated in antimicrobial resistance. Below are some examples of our work:

Nicotinic acetylcholine receptors

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Nicotine is the primary biologically psychoactive agent in tobacco, and it binds to neuronal nicotinic acetylcholine receptors (nAChRs). Currently, the FDA-approved anti-smoking compounds are only moderately effective in reducing the symptoms of nicotine withdrawal and may cause undesirable side effects. Currently, our work focuses on developing new agonists with improved nAChR subtype specificity and on identifying the molecular determinants that modulate ligand binding in each case. Interested in this topic? Read our latest publication “Understanding Varenicline Function via Key Receptor and Ligand Interactions”

Cytochrome c oxidase

Cytochrome c oxidases (CcOxs) are redox-driven proton pumps CCox_rotation-delay10 that use the free energy of oxygen reduction for the creation of a proton gradient across the membranes. Despite extensive experimental data available for this family, the molecular mechanisms underlying reduction and proton pumping remain largely unknown. Our main interest is understanding proton-pumping mechanisms at the molecular level. In particular, to identify the functionally relevant redox-induced conformational changes and how these affect proton pumping.

ATP-Binding Cassette transporters

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ATP-Binding Cassette (ABC) transporters are proteins that actively transport substrates across membranes. The specific conformational changes induced by ATP hydrolysis within the nucleotide-binding domains, and the mechanism by which these rearrangements are transmitted to the membrane domains, still remain mostly unresolved. Our research focuses on identifying these structural transitions and elucidating how the energy released from ATP hydrolysis is harnessed and propagated to the membrane domains to enable unidirectional substrate transport.

de novo designed redox proteins

As part of the BBSRC sLoLa grant “Circuits of Life“, our group is advancing the de novo design of heme-containing redox proteins. These engineered proteins aim to mimic and extendenature’s electron transfer capabilities, creating novel pathways for energy conversion and catalysis. By integrating principles of protein design with redox chemistry, we seek to build synthetic systems that illuminate fundamental biological processes and enable innovative biotechnological applications. Want to know more? See, for example, “Fluctuation Relations to Calculate Protein Redox Potentials from Molecular Dynamics Simulations“, “Delineating redox cooperativity in water-soluble and membrane multiheme cytochromes through protein design“, and “An expandable, modular de novo protein platform for precision redox engineering“

Selected Research Highlights

Upcoming in 2026

“pH-induced structural changes in SARS-CoV-2 spike variants” bioRxiv, DOI:10.1101/2025.11.17.688702
“Dynamical-nonequilibrium molecular dynamics (D-NEMD) simulations to investigate allostery and effects of mutations in biomolecular systems: a tutorial”, under review

2026

“Ligand-Driven Modulation of Chaperone–Cochaperone Networks Shapes Proteostasis Outcomes” Prot Sci, DOI: 10.1002/pro.70543
“Red-light-activated and thermally-stable amido-dithienylethenes for the reversible control of G-quadruplex binding and anticancer activity”, Bioorg Chem DOI: 10.1016/j.bioorg.2026.109710
“A dynamical-nonequilibrium molecular dynamics (D-NEMD) alanine scanning approach for identifying allosteric positions in proteins” Biophys J, accepted

2025

“Understanding Varenicline Function via Key Receptor and Ligand Interactions” Cell Rep Phys Sci, DOI:10.1016/j.xcrp.2025.102992
“Dynamic Behavior and Substrate Interactions of the Polymyxin Resistance Determinant MCR-1 Investigated by Extended Molecular Dynamics Simulations in the Membrane Environment” J Chem Inf Model, DOI:10.1021/acs.jcim.5c01338
“Activation mechanism of caseinolytic chaperone-protease system in Mycobacterium tuberculosis by the anti-cancer drug bortezomib” Nature Comms, DOI:10.1038/s41467-025-58410-4
“Bridged Azobenzene Exhibits Fully Reversible Photocontrolled Binding to a G-Quadruplex DNA/Duplex Junction” JACS Au, DOI:10.1021/jacsau.5c00532
“Allosteric modulation by the fatty acid site in the glycosylated SARS-CoV-2 spike” eLife, DOI:10.7554/eLife.97313

2024

“Decrypting the languages of allostery in membrane-bound K-Ras4B using four complementary in silico approaches” J Am Chem Soc, DOI:10.1021/jacs.3c11396
“Fluctuation Relations to Calculate Protein Redox Potentials from Molecular Dynamics Simulations” J Chem Theory Comput, DOI: https:10.1021/acs.jctc.3c00785
“Signal propagation in the ATPase domain of Mycobacterium tuberculosis DNA gyrase from dynamical-nonequilibrium molecular dynamics simulations” Biochemistry, DOI:10.1021/acs.biochem.4c00161
“Molecular Mechanisms of Glucocorticoid Receptor Chaperone Cycle: Insights from Atomistic Simulations” Prot Sci, DOI:10.1002/pro.4880
“Dynamical Responses Predict a Distal Site that Modulates Activity in an Antibiotic Resistance Enzyme” Chem Sci, DOI:10.1101/2024.04.29.591639

2023

“SARS-CoV-2 spike variants differ in their allosteric responses to linoleic acid” J Mol Cell Biol, DOI: https://doi.org/10.1101/2022.02.23.481608
“#COVIDisAirborne: AI-enabled multiscale computational microscopy of delta SARS-CoV-2 in a respiratory aerosol”Int J High Perform Comput Appl, DOI: https://doi.org/10.1177/10943420221128233
“Dynamical Nonequilibrium Molecular Dynamics Simulations Identify Allosteric Sites and Positions Associated with Drug Resistance in the SARS-CoV-2 Main Protease” JACS Au, DOI: https://doi.org/10.1021/jacsau.3c00185
“An expandable, modular de novo protein platform for precision redox engineering” Proc Natl Acad Sci, DOI: https://doi.org/10.1073/pnas.2306046120
“Heme binding to the SARS-CoV-2 spike glycoprotein” J Biol Chem, DOI: https://doi.org/10.1016/j.jbc.2023.105014

2022

“A Functional Interaction Between Y674-R685 Region of the SARS-CoV-2 Spike Protein and the Human α7 Nicotinic Receptor”, Mol Neurobiol, DOI: https://doi.org/10.1007/s12035-022-02947-8
“Structural insights in cell-type specific evolution of intra-host diversity by SARS-CoV-2”, Nat Commun. DOI: https://doi.org/10.1038/s41467-021-27881-6
“The fatty acid site is coupled to functional motifs in the SARS-CoV-2 spike protein and modulates spike allosteric behaviour”, Comput Struct Biotechnol J, DOI: https://doi.org/10.1016/j.csbj.2021.12.011

2021

“Dynamical nonequilibrium molecular dynamics reveals the structural basis for allostery and signal propagation in biomolecular systems”, Eur Phys J B, DOI: https://doi.org/10.1140/epjb/s10051-021-00157-0
“Allosteric communication in Class A β-lactamases occurs via Cooperative Coupling of Loop Dynamics”, eLife, DOI: https://doi.org/10.7554/eLife.66567
“A potential interaction between the SARS-CoV-2 spike protein and nicotinic acetylcholine receptors”, Biophys J, DOI: 10.1016/j.bpj.2021.01.037
“A conserved arginine with non‐conserved function is a key determinant of agonist selectivity in α7 nicotinic ACh receptors” Br J Pharmacol, DOI: https://doi.org/10.1111/bph.15389

2020

“F508del disturbs the dynamics of the nucleotide binding domains of CFTR before and after ATP hydrolysis”, Proteins, DOI: https://doi.org/10.1002/prot.25776

2019

“A general mechanism for signal propagation in the nicotinic acetylcholine receptor family”, J. Am. Chem. Soc, DOI:10.1021/jacs.9b09055
“Identification of the initial steps in signal transduction in the α4β2 nicotinic receptor: Insights from equilibrium and nonequilibrium simulations”, Structure, DOI: https://doi.org/10.1016/j.str.2019.04.008
“F508del disturbs the dynamics of the nucleotide binding domains of CFTR before and after ATP hydrolysis”, Proteins, DOI: https://doi.org/10.1002/prot.25776