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Center for Biotechnology and Interdisciplinary Studies - CBIS
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monteg3@rpi.edu
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518-276-4825
About
The unique strengths of our laboratory involve development of NMR methods and software for analysis of protein structures and dynamics, and in applying these methods in structure-function studies. As Director of the NIGMS-funded Northeast Structural Genomics Consortium (NESG) for 16 years (2000 – 2016), our lab lead a team that determined more than 1,200 3D structures by X-ray crystallography and NMR methods. Over the course of this project we developed expertise in protein expression and crystallization, and in reconstitution and structure determination of both soluble and integral membrane proteins. We also developed extensive experience in software development. The lab research programs span structural bioinformatics, protein expression and purification, X-ray crystallography, small-angle X-ray scattering (SAXS), and protein NMR with applications in cancer biology, virology, de novo protein design, integral membrane proteins, and drug development.
Research
Our laboratory research program revolves around the themes of new technology development for protein structure production and computational analysis. Based on our experience as a central node for protein sample production and structure determination by NMR in the NIGMS PSI program, rigorous structure and dynamic analysis of small (< 15 kDa) proteins in our laboratory is largely automated and routine. However, most of our current research program focus on larger (> 20 kDa), more challenging systems, including integral membrane proteins and protein complexes. These projects require hybrid approaches, combining NMR data with X-ray crystallography, SAXS, paramagnetic NMR and EPR, and other biophysical methods, along with advanced computational modeling and structural bioinformatics. In order to ensure rigor in applying this broad range of methods, we collaborate intensively with internationally-recognized experts in these domains. For example, we work with experts to explore the impact of Evolutionary Coupling (C. Sander, D. Marks), Rosetta (D. Baker), and CHARMM (W. Im) modeling methods for determining 3D structures of larger proteins for which only sparse, incomplete experimental data is available, including integral membrane proteins. We also rely on our collaborators in paramagnetic NMR (C. Luchinat and G Parigi), SAXS (J. Tainer), fluorescence spectroscopy (C. Royer), EPR (M. Kennedy), and cryoEM (J. Hunt, K. Das) to provide expertise in these critical experimental methods. We also lead the structural biology components of several biomedical collaborations, including projects on viral-host protein/RNA interactions of influenza (with S. Patel, Rutgers) and murine leukemia (with M. Roth, Rutgers) viruses, SARS-CoV2 inhibitor development (with A. Garcia-Sastre, Mt. Sinai), DNA damage repair (with S. Bunting, Rutgers), and de novo protein design (with D. Baker, U Wash.). We also collaborate with the Critical Assessment of Protein Structure Prediction (CASP) program to organize efforts in sparse-NMR-guided structure prediction across the CASP community and AI-based methods for modeling multiple conformations of proteins, and with the wwPDB to develop robust and rigorous methods of protein and nucleic acid structure quality assessment. All of these collaborations are aimed at ensuring the highest rigor and quality control, and in addressing important biomedical questions.
structural bioinformatics, host - pathogen interactions, protein structure, dynamics, and function, biomolecular NMR spectroscopy, molecular biophysics, integral membrane proteins
Publications
The following is a selection of recent publications in Scopus. Gaetano Montelione has 396 indexed publications in the subjects of Biochemistry, Genetics and Molecular Biology, Chemistry, Medicine.