Research Areas

3D-EM Model Validation and Refinement  

Our group focuses on developing tools for image processing, fitting, and assessing atomic models in cryo-EM maps. These methods are used to characterize macromolecular assemblies. Recently, we developed the TEMPy-ReFF software for the refinement of atomic models in cryo-EM maps using a Gaussian Mixture Model (GMM). This method has been used to refine and assess models submitted for CASP15 cryo-EM targets, including RNA targets. We also developed ChemEM for the fitting and refinement of small molecules in cryo-EM maps.  

Beton*, Mulvaney* et al, Nat Commun 2024; Sweeney et al, J Med Chem 2024

Mass Spectrometry-based Modelling

We developed various methods to assess models of protein structures based on cross-links and mono-links derived from mass spectrometry. Our most recent method for calculating cross-link/mono-link-based model scores is called XLMS-tools. Our methodology, guided by these scores, has proven effective in identifying accurate models within AlphaFold2 ensembles. 

Manalastas-Kantos et al, Mol Cell Proteomics 2024 

Protein-Protein Interaction Networks  

We use protein-protein interaction (PPI) network analysis to provide new functional characterizations of virus families. We developed a computational framework for PPI network assembly, which combines both experimentally validated and computationally predicted PPI data. Using this framework, we created system-level compilations of the binary interactions among virally-encoded proteins. We applied it to three different species of human herpesviruses. Using a consensus clustering approach, we studied the community structure of the network data and revealed higher-order functional associations among viral proteins. Combined with AlphaFold2 assembly modeling and interface analysis by PI-score and PICKLUSTER, we can model direct interactions predicted in our networks. 

Hernández et al, PLoS Biol 2019; Malhotra et al, Nat Comm 2021; Genz et al. Bioinformatics 2023