With the prospect of new exascale facilities, chemistry is nowadays studied also using computer resources. Large-scale simulations are continuously growing and being more and more efficient in predicting what will happen in a tube before the experiments will be carried out.
This is the aim of our research: predicting through advanced sampling molecular simulations the molecular mechanisms, making efficient a given chemical process. We are actually focused on the nanoscale simulations and chemical modeling, with a particular attention on the efficiency of macromolecular switches upon irradiation, small ligand binding or coordination with metals. The stereochemical effects on the macromolecular structures leading to the observed chiroptical properties are also objects of our research studies. With this purpose, a continuos development of computational chemistry methods and algorithms are subjects of our research interest.
In the following you can find a summary of the actual research lines.
Chiral switch frameworks
The chiral switch properties of macromolecular frameworks under light irradiation are here investigated. We aim at combining new strategies for developing bespoke chiral switches with tailored activation barriers.
We identified the mechanism of chirality inversion in helical switches through the estimation of the free-energy landscape (Pietropaolo and Nakano J. Am. Chem. Soc. 2013 135, 5509–5512).
We also predicted the efficiency of macromolecular switches in polyfluorene derivatives under circularly polarized light irradiation through a stepwise switching of the fluorene-fluorene dihedrals. We found out a particular role of the inert support for devising the chiral switch cycle, which is only allowed when the polymer is deposited on amorphous silica (Pietropaolo, Yue, Nakano Angew. Chem. Int. Ed. 2015 54,2688-2692). We here use the chiral path coordinates (Pietropaolo, Branduardi, Bonomi, Parrinello J Comput Chem 2011 32, 2627-2637) based on a chiral descriptor designed for disclosing helix handedness (Pietropaolo, Muccioli, Berardi, Zannoni Proteins 2008, 2008, 70, 667-677; Pietropaolo and Parrinello Chirality 2011, 23, 534-542).
Optical properties and spectra calculations
All the free-energy simulation results are carefully evaluated owing to close collaborations with experimental groups. An example is shown from the back calculations of ECD spectra from the enantiomeric free-energy basins of the fluorene-based polymers published in Pietropaolo, Yue, Nakano Angew. Chem. Int. Ed. 2015 54,2688-2692. Time-dependent UV spectra compared to those obtained with TD-DFT methods also showed a very accurate prediction, explaining the hypochromism and blue-shift obtained with circularly polarized light irradiation.
Stereoselectivity and conformational switch under metal coordination
We have quantitatively explained the observed stereoselectivity in copper-glycopetide frameworks with L- and D- aminoacids by using free energy methods combined with free energy perturbation theory. We determined the free energy of binding between the carbohydrate and the D/L metal core for the two frameworks, considering that upon removing the carbohydrate unit, the D/L metal cores become enantiomers. In order to quantify the chemical stereoselectivity we used free energy perturbation theory reconstructing the free energy of binding landscape between Trehalose and the metal core in L and D diastereoisomers. A parameter on the harmonic potential was introduced in order to explore unbound and bound states, thereby estimating the free energy surface including correction term for accounting the extra-harmonic potential. The difference of those free energy landscape is in line with the ratio of the two stability constants. (Grasso et al. Chem Eur J 2011 17:4778)
We use ab-initio methods in order to predict the structure of transition metal complexes coordinated to protein sections. We are actually investigating the conformational switching upon metal binding (Travaglia et al. Chem. Eur. J. 2012 18:15618), (Grasso et al. Chem Eur J 2011, 17:2752-2762.)
Conformational switch under substrate binding
The switching mechanism of the ADP/ATP carrier (AAC) was elucidated through free-energy simulations, shedding light on the c-, intermediate and m-state conformations of the AAC. The carrier recognizes its substrate via a three-state mechanism. In particular, when the substrate is uncorrect, an intermediate-state is adopted, preventing the transition to the m-state conformation.