Protein Dynamics group, led by Prof. Francesco Luigi Gervasio, focusses on the development of methods for biomolecular simulations with emphasis on enhanced sampling methods, as well as multiscale and coarse-grained models. The group crucially contributed to the development of methods for overcoming the timescale problem (metadynamics, parallel-tempering metadynamics, path collective variables, SWISH), which are widely used across different fields ranging from nanotechnology to biophysics.

We apply these methods to study a multitude of complex biophysical phenomena, including protein dynamics and folding, ligand binding, allosteric mechanisms, and modes of action of cancer-causing mutations. Our simulations have guided the design of several allosteric inhibitors that are now in pre-clinical development as anticancer drugs. Furthermore, we have a fruitful line of experimental research (NMR, SPR, mutagenesis) to validate the computational predictions, as well as active collaborations with pharmaceutical companies (Astra Zeneca, Evotec, Heptares, and UCB).

New paper on the binding mechanism of retinol to CRBP-I and CRBP-II

Here, we unravel the binding mechanism of retitol to the two most abundant retinol-binding isoforms, CRBP-I and CRBP-II, using enhanced sampling molecular dynamics simulations and surface…

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New paper on the role of post-translational modification on Htt(1-19)

We used Molecular Dynamics simulations with a novel Hamiltonian-replica-exchange-based enhanced sampling method, SWISH, and an optimal combination of water and protein force fields to study…

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New paper on the selectivity of ligands in a GPCR family

Using enhanced sampling simulations we identify the determinants of selectivity of ligands in A2a and A1 adenosine receptors. Mattedi, G., Deflorian, F., Mason, J. S., de Graaf,…

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