The Structural Bioinformatics Laboratory at Rensselaer Polytechnic Institute investigates the structural dynamics underlying protein function. Our work utilizes a combination of computational methods and biophysical data to elucidate mechanisms of biological processes.
Research Highlights
Design of intrinsically disordered region binding proteins (July 2025)
In this new Science paper, our collaborators in the Baker lab used AI-guided design to create proteins that bind tightly and specifically to 39 disordered targets, including the opioid peptide dynorphin, cancer-related receptor regions, and prion-like viral sequences. Together with X-ray crystallography, our lab validated the dynorphin binders by NMR, confirming that binding locks the flexible peptide into a defined shape. This modular method can be used to design binding proteins for virtually any disordered protein or peptide target allowing for the ability to now target the “untargetable”.
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.
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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