RPI Structural Bioinformatics Lab
A structural bioinformatics laboratory at Rensselaer Polytechnic Institute investigating 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.
Milestones
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 Tuesday Jan 7, 2025.
Graduate student Rebecca Greene-Cramer has been awarded the 2024 Slezak Memorial Fellowship. This fellowship is awarded to a 3rd or 4th year RPI chemistry graduate student who has an excellent academic record and has shown outstanding research performance. Congratulations Rebecca!!
Congratulations to Reena Caplan, Alexander White, and Suren Zakian who have each been awarded a Chemistry Summer Undergraduate Research Program (C-SURP) Fellowship to pursue research projects in our lab in the summer 2024.
April 2024
Montelione Lab Research Associate, Anna De Falco, PhD presented “A platform of Viral Protease Inhibitor Characterization” at Scripps Research Institute in La Jolla, California in early April 2024.
This poster is an updated summary of ongoing work conducted by the Montelione and Cioffi Labs at RPI over the last 2 years. This collaboration with Scripps Institute Center for Antiviral Medicines and Pandemic Preparedness (CAMPP) is one of nine NIAID-sponsored Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern. Excellent job representing the group at the annual meeting, Dr. De Falco!
