Radiotracers4PSMA

Despite possessing a range of computational resources, the consortium has limited capacity to fully develop this project using advanced computational approaches due to the complexity of the target and the difficulty associated with performing exhaustive molecular dynamics simulations to explore binding events over long timescales. The EGI Federation aims to empower researchers from all disciplines to collaborate in data- and compute-intensive research by providing free-at-point-of-use services. EGI offers computing and storage resources, compute platform services, data management services, and dedicated user support, which other providers do not have. Consequently, applying to use the EGI infrastructure was a logical choice.

Radiotracers4PSMA is using the following EGI services:

•  The EGI Cloud Compute service has been used to deploy a VM equipped with suitable computational resources aimed at implementing the research project activities. Through the cloud compute service, it has been possible to implement a powerful VM equipped with four GPUs NVIDIA A40 required to run the molecular dynamic simulations. The cloud platform allows users to easily deploy the VM using a pre-loaded image that has been properly used and configured for the aim of the project. 
• Thanks to the cloud based EGI online storage service, the research team was able to take advantage of 170 TB of space to store the complex molecular dynamics simulations.
• The EGI check-in is used to access the cloud platform with the aim to configure the VM according to the needs of the research team. 

A consortium of three Italian research teams, working at the Institute of Biomedical Technologies of the National Research Council (CNR-ITB), at the University of Genoa (UniGe) and the Nuclear Medicine Unity at Dissal-Unige and IRCCS Ospedale Policlinico San Martino, Genoa is using computational time from the EGI Federation (awarded through the EGI access call) to support investigational studies on the molecular mechanism of action of theranostic probes for Prostate-specific membrane antigen PSMA. The insights gained from this computational study could provide key atomistic details to design new and more efficient theranostic agents for prostate cancer diagnosis and patient follow-up.

The consortium combines expertise from different areas (Bioinformatics, Biochemistry, Medicinal Chemistry and Nuclear Medicine). It is composed of three Italian research teams: the first team is part of the bioinformatics laboratory at the Institute of Biomedical Technologies of the National Research Council (CNR-ITB) whose members (Pasqualina D’Ursi, Andrea Manconi, Gabriele Trombetti) have matured consolidated skills in the field of molecular modelling and drug discovery (PD) as well as in the implementation and maintenance of specialised bioinformatics infrastructures (AM, GT), participating in several National and European projects. The second team is part of the Department of Pharmacy, University of Genoa, and its senior scientist (Paola Fossa) has solid drug discovery and drug design expertise. The two teams strongly interact since they have collaborated for more than ten years on several pharmaceutical topics like the design and development of cyclic nucleotides phosphodiesterases PDE4 inhibitors and new drugs for cystic fibrosis treatment. The third team, the Nuclear Medicine Unity at Dissal-Unige and IRCCS Ospedale Policlinico San Martino, Genoa, directed by Prof. GianMario Sambuceti (GianMario Sambuceti, Matteo Bauckneht, Mattia Riondato) joins the fundamental and consolidated expertise on theranostic agents application in clinic (GMS, MB) with the knowledge on radioactive drugs synthetic procedures and manipulation (MR). 

Prof. Marco Rusnati, University of Brescia, is a partner in the project and is in charge of Surface Plasmon Resonance determinations planned to experimentally validate the in silico findings.

The present activity involves the training in drug discovery studies and advanced biosimulations of three young researchers (PhD student Beatrice Casini, MS students Miriana Vezzoli and Luca Rizzi); and results from this use case have been shared and will be shared with the scientific community through public repositories, poster communications and oral communications at meetings.

The project timeline spans from December 2023 through December 2025.