
The Structural Bioinformatics Laboratory at Rensselaer Polytechnic Institute investigates the structural dynamics underlying protein function. Our work is a combination of computational methods using biophysical data to elucidate mechanisms of biological processes.
Research Highlights
This manuscript details the application of Isothermal Titration Calorimetry (ITC) to characterize the kinetics of 3CLpro, the main protease from the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2), and its inhibition by Ensitrelvir, a known non-covalent inhibitor. 3CLpro is essential for producing the proteins necessary for viral infection, which led to the COVID-19 pandemic. The ITC-based assay provided rapid and reliable measurements of 3CLpro activity, allowing for the direct derivation of the kinetic enzymatic constants KM and kcat by monitoring the thermal power required to maintain a constant temperature as the substrate is consumed.
Blind assessment of monomeric AlphaFold2 protein structure models with experimental NMR data
Recent advances in molecular modeling of protein structures are changing the field of structural biology. AlphaFold-2 (AF2), an AI system developed by DeepMind, Inc., utilizes attention-based deep learning to predict models of protein structures with high accuracy. Since AF2 was trained on X-ray crystal and cryoEM structures, we assessed how accurately AF2 can model small, monomeric, solution protein NMR structures which (i) were not used in the AF2 training data set, and (ii) did not have homologous structures in the Protein Data Bank at the time of AF2 training. In most of the cases investigated, the AF2 models fit the NMR data nearly as well, or sometimes better than, the corresponding NMR structure models previously deposited in the Protein Data Bank. These results provide benchmark NMR data for assessing new NMR data analysis and protein structure prediction methods.
Rebecca Greene-Cramer was recognized as a Future Leader at the Eastern New York Chapter of the American Chemistry Society. She also received First Place, 3 Minute Thesis (3MT) – Rensselaer Polytechnic Institute in April 2025, and was awarded the Bauer Prize for Best Ph.D. Thesis in Chemistry.

Congratulations to Laura Spaman for Best Oral Presentation at the Chemistry Graduate Student Symposium for her scientific talk titled: “AlphaFold2 and Experimental Biophysics: A Synergistic Approach to Understanding Protein Structure and Behavior,” on Jan 7, 2025.

May 2025

Congratulations to Dr. Rebecca Greene-Cramer for completing a Ph.D. in Chemistry and Chemical Biology, titled “The Pursuit of Broad-Spectrum Antivirals: Leveraging Structural Insights into Viral Proteases”

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