Molecular recognition, binding and catalysis are fundamental processes in cell function. The ability to understand how macromolecules interact with their binding partners and participate in complex cellular networks is crucial to prediction of macromolecular function, and to applications such as protein engineering and structure-based drug design.

The Molecular and Cellular Modeling (MCM) group works on the development and application of computer-aided methods to predict and simulate biomolecular interactions. The focus is on proteins and our computational approaches are mostly based on the three-dimensional structures of macromolecules. Techniques cover a wide spectrum from interactive, web-based visualization tools to molecular and Brownian dynamics simulations.

Selected recent publications
Original Papers

Beccaria R, Muñiz-Chicharro A, Wade RC. Multiscale Brownian dynamics simulations reveal effects of macromolecular crowding on protein-ligand association, Proc. Natl. Acad. Sci. U.S.A.  2026 in press.

Milanesi M, Urbinati C, Zimmermann L, Oreste P, Zani A, Caruso A, Caccuri F, Laketa V, Chlanda P, Wade RC, Rusnati M, Paiardi G. K5 polysaccharides inhibit SARS-CoV-2 infection by preventing spike-proteolytic priming, npj Viruses 2026; 4(1):3.

Kehr D, Ritterhoff J, Glaser M, Jarosch L, Salazar RE, Spaich K, Varadi K, Birkenstock J, Egger M, Gao E, Koch WJ, Sauter M, Freichel M, Katus HA, Frey N, Jungmann A, Busch C, Mather PJ, Ruhparwar A, Busch M, Völkers M, Wade RC, Most P. S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models, Circulation 2025; 151(8):548-565.

Paiardi G, Ferraz M, Rusnati M, Wade RC. The accomplices: Heparan sulfates and N-glycans foster SARS-CoV-2 spike:ACE2 receptor binding and virus priming, Proc. Natl. Acad. Sci. U.S.A. 2024; 121(43):e2404892121.

D’Arrigo G, Kokh DB, Nunes-Alves A, Wade RC Computational screening of the effects of mutations on protein-protein off-rates and dissociation mechanisms by τRAMD, Commun Biol 2024; 7(1):1159.

Cabezudo AC, Athanasiou C, Tsengenes A, Wade RC. Scaling Protein–Water Interactions in the Martini 3 Coarse-Grained Force Field to Simulate Transmembrane Helix Dimers in Different Lipid Environments, J. Chem. Theory Comput. 2023; 19, 2109-2119, doi: 10.1021/acs.jctc.2c00950

Nunes-Alves A, Kokh DB, Wade RC (2021). Ligand unbinding mechanisms and kinetics for T4 lysozyme mutants from τRAMD simulations, Current Research in Structural Biology 3:106-111

Berger B, Amaral M, Kokh DB, Nunes-Alves A, Musil D, Heinrich T, Schröder M, Neil R, Wang J, Navratilova I, Bomke J, Elkins JM, Müller S, Frech M, Wade RC, Knapp S (2021). Structure-kinetic relationship reveals the mechanism of selectivity of FAK inhibitors over PYK2, Cell Chemical Biology,S2451945621000039

Mukherjee G, Nandekar PP, Wade RC (2021). An electron transfer competent structural ensemble of membrane-bound cytochrome P450 1A1 and cytochrome P450 oxidoreductase, Commun Biol 4:55

Yuan J, Han SB, Richter S, Wade RC, Kokh DB (2020). Druggability Assessment in TRAPP Using Machine Learning Approaches, J. Chem. Inf. Model. 60(3):1685-1699

Bruce NJ, Narzi D, Trpevski D, Keulen SCv, Nair AG, Röthlisberger U, Wade RC, Carloni P, Kotaleski JH (2019). Regulation of adenylyl cyclase 5 in striatal neurons confers the ability to detect coincident neuromodulatory signals, PLoS Comput Biol 15(10):e1007382

Öztürk MA, Cojocaru V, Wade RC (2018). Toward an Ensemble View of Chromatosome Structure: A Paradigm Shift from One to Many, Structure 26(8):1050-1057

Douglas RG, Nandekar P, Aktories J, Kumar H, Weber R, Sattler JM, Singer M, Lepper S, Sadiq SK, Wade RC, Frischknecht F (2018). Inter-subunit interactions drive divergent dynamics in mammalian and Plasmodium actin filaments, PLoS Biol 16(7):e2005345

Kokh DB, Amaral M, Bomke J, Grädler U, Musil D, Buchstaller H, Dreyer MK, Frech M, Lowinski M, Vallee F, Bianciotto M, Rak A, Wade RC (2018). Estimation of Drug-Target Residence Times by τ-Random Acceleration Molecular Dynamics Simulations, J. Chem. Theory Comput. 14(7):3859-3869

Amaral M, Kokh DB, Bomke J, Wegener A, Buchstaller HP, Eggenweiler HM, Matias P, Sirrenberg C, Wade RC, Frech M (2017). Protein conformational flexibility modulates kinetics and thermodynamics of drug binding, Nat Commun 8(1),2276

Nillegoda NB, Stank A, Malinverni D, Alberts N, Szlachcic A, Barducci A, Rios PDL, Wade RC, Bukau B (2017). Evolution of an intricate J-protein network driving protein disaggregation in eukaryotes., eLife 6,e24560

Reviews

Wolf S, Bottegoni G, Nunes-Alves A, Wade RC. Where do we go from here? Current state of drug-target binding kinetics and a roadmap to their establishment in drug discovery campaigns, Drug Discovery Today 2026; 31, 104704. 

Muñiz-Chicharro A, Votapka LW, Amaro RE, Wade RC. Brownian dynamics simulations of biomolecular diffusional association processes, WIREs Comput Mol Sci2023; 13:e1649. doi: 10.1002/wcms.1649

Nunes-Alves A, Kokh DB, Wade RC (2020). Recent progress in molecular simulation methods for drug binding kinetics, Current Opinion in Structural Biology 64:126-133

Öztürk MA, De M, Cojocaru V, Wade RC (2020). Chromatosome Structure and Dynamics from Molecular Simulations, Annu. Rev. Phys. Chem. 71(1):101-119

Bruce NJ, Ganotra GK, Kokh DB, Sadiq SK, Wade RC (2018). New approaches for computing ligand–receptor binding kinetics, Current Opinion in Structural Biology 49:1-10

Stank A, Kokh DB, Fuller JC, Wade RC (2016). Protein Binding Pocket Dynamics, Acc. Chem. Res. 49(5):809-815

Ozboyaci M, Kokh DB, Corni S, Wade RC (2016). Modeling and simulation of protein–surface interactions: achievements and challenges, Quart. Rev. Biophys. 49,e4