Professor Whitford’s research probes the energetic properties of biomolecular dynamics through a combination of theoretical modeling and high-performance computing (HPC). His investigations of biomolecular order-disorder transitions and energy transduction processes span from protein and ribonucleic acid folding, to large-scale conformational rearrangements in molecular machines. Since this work is at the interface of statistical mechanics, and areas of chemical and biological research, many investigations are performed in close collaboration with experimental researchers, which allows for quantitative comparisons of theoretical concepts and cellular dynamics.
The principal class of models that they use for simulating biomolecules are Structure-Based Models. Grounded by experimental observables, these models approximate the effective energy landscape of a molecule by a single (or a few) dominant basin of attraction. It is then possible to systematically analyze the response of the system to perturbations, which can mimic drug interactions, changes in cellular conditions, the formation of biomolecular interfaces and energy-releasing chemical steps. From this, they are identifying the essential energy landscape features that are responsible for biological function.
Recent Publications
Transient ion-mediated interactions regulate subunit rotation in a eukaryotic ribosome
G Wanes, U Mohanty, and P C Whitford.
Proceedings of the National Academy of Sciences USA, 2026. DOI: 10.1073/pnas.2527693123
Structure and inhibition of SARS-CoV-2 spike refolding in membranes
M W Grunst, Z Qin, E Dodero-Rojas, S Ding, J Prévost, Y Chen, Y Hu, M Pazgier, S Wu, X Xie, A Finzi, J N Onuchic, P C Whitford, W Mothes, and W Li.
Science, 385, 757-765, 2024. DOI: 10.1126/science.adn5658
Getting gene expression “just right”
P C Whitford.
Proceedings of the National Academy of Sciences USA, 122, e2529119122, 2025. DOI: 10.1073/pnas.2529119122
Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk
V Singh, Y Itoh, S Del’Olio, A Hassan, A Naschberger, R K Flygaard, Y Nobe, K Izumikawa, S Aibara, J Andrell, P C Whitford, A Barrientos, M Taoka, and A Amunts.
Nature Communications, 15, 4272, 2024. DOI: 10.1038/s41467-024-48163-x
Diffuse ions coordinate dynamics in a ribonucleoprotein assembly
A Wang, M Levi, U Mohanty, and P C Whitford.
Journal of the American Chemical Society, 144, 9510-9522, 2022. DOI: 10.1021/jacs.2c04082
Awards & Recognition
- NSF CAREER Award
In The News
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Research
New insight into antibody shows how it could offer sweeping protection against evolving SARS-CoV-2 virus
The results suggest that the neutralizing antibody could hold the key to manufacturing a vaccine that protects against a rapidly evolving virus. -
Research
No needles? No problem. This COVID-19 vaccine could be inhaled.
Paul Whitford and a team of scientists develop an inhalable vaccine strategy in the hopes of offering a simple and efficient way of administering COVID-19 vaccines. -
Research
The Ribosome: Is it the Key to the Next Generation of Antibiotic Therapies?
This article highlights the research done by the Whitford lab that was recently published in the journal Nature. Using high-performance computer modeling, the research group identified a target location on the ribosome that elucidates a potential for antibiotic therapies.