(231h) Coupled Computational/Experimental Approach to the Thermodynamics of Biomolecular Interaction

The nano(bio)molecular technology covers both synthetic or natural systems with nanometric size or the functionality of the relevant components on the nanometer scale, which results in new and unique properties of the material. This branch of science occupies now a prosperous niche in medicine, known as nanomedicine, in particular in the field of transport and controlled release of therapeutic agents through the use of nano-engineered carriers. It is estimated that several hundred different nanocarriers are in pre-clinical and clinical development throughout the world. These nanometer-sized molecular entities have the primary function of transporting the active agent to the target site, protecting it from degradation and allowing his safe crossing through the biological barriers. To achieve these ambitious goals, however, the nanocarriers have to be carefully designed and manufactured and the thermodynamics that drives their relationship with the biological target amount is one of the fundamental aspects that must be studied in detail during the design process. In this work we present case studies of a thorough investigation of the interaction between different nanocarriers and the related biological targets using a combination of computational and experimental techniques [1-4]. In detail, different molecular simulation computer aided methodologies have been employed to determine the binding mode of the nanovector/target complex and the corresponding thermodynamic parameters. All the molecular determinants that contribute to the free energy of binding were analyzed by quantifying also the structural changes induced by the formation of the complex. All properties and behaviours predicted by molecular simulations have been validated using different experimental approaches, including the isothermal titration calorimetry (ITC) and fluorescence.

[1] C.W. Chan et al. Chem. Comm. 52, 10540 (2017)

[2] A.C. Rodrigo et al. Chem. Comm. 53, 11580 (2017)

[3] K.A. Thornalley et al.Angewandte Chemie – Int. Ed. 57, 8530 (2018)

[4] E. Laurini et al. Fluid Phase Equilibria 470, 259 (2018)