Mobility experience with a research focus
Master students involved in the final research, PhD sandwich, Post Doc
Dept. Pharmaceutical and Pharmacological Sciences – Molecular Modeling Section (MMS), University of Padua
Title: New computational methodologies in inspecting ligand-receptor recognition pathways and ligand-receptor complexes stability: a combo strategy to speed up the identification of drug candidates.
Topics: One of the most challenging issues for the future of drug discovery is the capability to understand the receptor-ligand recognition pathway and their complexes stability, with the aim to facilitate the development of drug candidates with more favourable pharmacodynamic profiles. Unfortunately, the recognition process between a ligand and receptor, and its residence time, are a very complex events to describe at the molecular level, and even with the recent GPU-based computing resources, it is necessary to carry out classical molecular dynamics (MD) experiments in a long microsecond time scale. To overcome this limiting factor, we have implemented an alternative MD approach, named supervised molecular dynamics (SuMD), that enables us to follow receptor-ligand approaching process within a time scale reduced up to 3 orders of magnitude compared to classical MD. SuMD enables the investigation of ligand-receptor binding events independently from the starting position, chemical structure of the ligand, and also from its receptor binding affinity. Moreover, recently, there has been a paradigm shift, with an increased interest in the determination of kinetic properties such as the drug-target residence time since they better correlate with ligand efficacy compared to other parameters. We have implemented a thermal titration molecular dynamics (TTMD), an alternative computational method that combines a series of molecular dynamics simulations performed at progressively increasing temperatures with a scoring function based on protein-ligand interaction fingerprints for the qualitative estimation of protein-ligand-binding stability.
Objectives: Theme A – Application of SuMD technology in different hot therapeutic area such as oncology, inflammation and immunology. Theme B – Application of TTMD technology in different hot therapeutic area such as oncology, inflammation and immunology.
Background in Chemistry, Medicinal Chemistry, Pharmacy and Biotechnologies with a basic knowledge in informatics. A plus should be a good knowledge in informatics (linux environments) and solid skills in Phyton programming.
Master research: 3-6
PhD sandwich: 6-12
Post Doc: 6-12