PhD studentship: Understanding the impact of conformational complexity on the crystallizability of APIs with molecular simulations and data-science methods

UCL

Expected to start in February 2021 or as soon as possible

This studentship is focussed on the application and development of molecular dynamics and data science methods to investigate the role of conformational complexity in the definition of crystallizability of Active Pharmaceutical Ingredients (APIs). The PhD project is partially funded by, and in collaboration with Pfizer.
Leveraging recent results obtained within the context of a collaboration between Pfizer and the Molecular Modelling and Engineering group at UCL Chemical Engineering we propose to combine enhanced sampling simulation methods, and unsupervised clustering approaches to develop systematic computational protocols that will enable to identify conformational states for complex molecules in explicit solution, to evaluate their relative free energy accounting for solvent conformational entropy contributions, and to identify conformational kinetic bottlenecks that may be responsible for inducing conformational polymorphism or hindering altogether the crystallizability of an API. The adoption of data-driven strategies for the analysis of the conformational space of complex APIs will represent a key aspect of this project.

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