I have experience in the development and application of computational algorithms in the field of proteins in aqueous solution. Since my PhD, I have been programming many different codes in Fortran, C++ or bash for the description of the structural dynamics of proteins. In collaboration with Prof.Laio (SISSA, Italy), I have developed the algorithm for the design of nanobodies as binders of protein targets. My background in chemistry, computational chemistry and biophysics applied to protein systems offers me the unique opportunity to cover a wide range of problems and applications in the research field of proteins. My research goes through the study of vibrational relaxation of peptides (Murcia), the protein folding (Lisbon), and protein-protein interaction (Italy). Therefore, my expertise is often required in my work for disentangle this intriguing triangular relationship among dynamics-structure-function that regulates the biological role of proteins. In the present, I am carrying on new projects in Genova, always in the field of protein biophysics and medicine, while I continue my collaboration in the protein design field. On one hand, I am working in a project for the development of broad-spectrum vaccines for Dengue and Zika in collaboration with Dr. Burrone (ICGEB) based on the in silico design of anti-idiotypic antibodies, which has been awarded in the 19th PRACE call. Moreover, I am currently broadening my knowledge in computational structural biology within the project in collaboration with the Institute of Cancer Research (UK) focused on the study of mechanisms for the regulation of the activity of protein cancer targets.
Design of anti-idiotypic antibody fragments as vaccines.
In this project we exploit the PRACE HPC resources awarded this year 2019 with our recently developed evolutionary algorithm of binder design to produce immuno-agents with the capability of being employed as broad-spectrum vaccines for Zika (ZIKV) and all serotypes of Dengue virus (DENV). Thus, we propose a protocol of in silico mutagenesis coupled to affinity and selectivity screening in order to test the anti-idiotypic antibody hypothesis, i.e. the capability of an antibody directed against the binding regions of another antibody (anti-A) to mimic the molecular features of the original antigen A. Our group in collaboration with our experimental partner, the Laboratory of Molecular Immunology of ICGEB in Trieste, led by Prof. Oscar Burrone, already identified a preliminary molecular construct, at present under experimental testing, exposing 2 out of the 4 main epitopes responsible for the binding of EDE with the EDE1-C8 antibody.
Recently awarded with PRACE 2019 Call (19,700,000 core hours, W. Rocchia and M.A. Soler).
Current collaborators include: Oscar Burrone (ICGEB, Italy), Ario DeMarco (University of Nova Gorica,
Enhanced sampling MD simulations for studying protein functionality
Most interesting molecular phenomena in proteins often occur on a timescale which is out of reach for conventional "brute force" Molecular Dynamics (MD) simulation. Enhanced Sampling techniques act so as to achieve a statistically significant sampling of relevant regions of the conformational space, allowing the study of the mechanisms that control the biological role of proteins and the development of strategies for the modulation of the protein activity. For instance, we currently collaborate with the group of Computational Structural Biology in the Institute of Cancer Research Institute (UK) to discover cryptic allosteric epitopes for the regulation of protein cancer targets.
Current external collaborators include: Bissan Al-Lazikani, Patrizio Di Micco (ICR, UK).
Different computational protocols for evaluating with more accuracy and more efficiently the binding affinity of protein-protein complexes have been developed during the last period, as well as new approaches to predict the stability of the engineered nanobodies. This methodologies resulted essential for the optimal performance of the in silico design of protein binders with enhanced affinities. Nowadays, the design of nanobodies for the molecular recognition of HER2, the most famous mammalian cancer biomarker, have been performed and are being produced and analyzed for their affinity and stability in an iterative two-way transfer between empiric data and theoretical modelling. My research involves the selection of new protein targets related with diseases which allows extending the application of the designed nanobodies to the diagnosis and prognosis and to therapeutical drugs.
Recently awarded with ARDF Annual Open Grant 2019 ($39,980 US, S. Fortuna and M.A. Soler).
Current external collaborators include: Alessandro Laio (SISSA, Trieste, IT), Ario DeMarco (University of Nova Gorica, Slovenia), Loredana Casalis (Elettra, Trieste, IT) , Sara Fortuna (Univ. Trieste, IT).