PhD Position in rational drug design of intrinsically disordered proteins

Academic supervisor:

Prof. Gianni De Fabritiis


Coordination of cellular processes requires time-ordered formation of functional complexes for which the proper timing of binding and unbinding is critical. Although evidence exists for the relevance of kinetics for biological function, the underlying physical-chemistry mechanisms are still largely unexplored. This is especially true for protein domains without a native folded conformation as, in absence of a structured state, a shift of the equilibrium towards active or inactive states may not be feasible.

Using massively distributed molecular dynamics simulations, high performance codes and new Markov state analytical tools, all largely developed by us, we have shown in a series of pilot studies the capability to resolve molecular kinetics once the multi-millisecond timescale is reached. Preliminary mathematical kinetic models also show that, by modulating the molecular kinetics of competing on-pathway metastable states, it is possible to control the equilibrium of the complex, a novel and potentially important mechanism for intrinsically disordered proteins.

In this project, we aim to investigate the relevance and generality of molecular kinetics for intrinsically disordered protein domains and its modulation by small molecules. We will employ a computationally driven approach to resolve kinetics at atomic resolution, and will integrate our computational predictions with standard assays and experiments from collaborations with experimental experts and local facilities.

We expect the candidate to participate in the design and implementation of computational protocols to using the advanced computational developed in the group.


Barcelona, Spain,Barcelona Biomedical Research park. The GRIB/UPF is part of the new Barcelona Biomedical Research Park which, with a privileged location on the shoreline of the Mediterranean sea, constitutes one of the most exciting interdisciplinary research centres in Southern Europe in one of the fastest growing biomedical research regions in the continent with over a thousand scientists.

Candidate Profile:

The candidate will preferably have a profile in biochemistry, chemistry, pharmaceutics, biotechnology, biology. We also have in our group students with a background in computer science, physics, mathematics. Very good communication skills in English are required.


The candidate will be able to use which gives the possibility to run high throughput molecular dynamics simulations of multi millisecond timescales routinely. The laboratory is very well equipped with also access to a local GPU cluster and experimental facilities to measure affinities and kinetics.

The molecular modelling will be using state of the art software environments in molecular modelling and simulations ( developed by the research group in collaboration with Acellera (

Funding and Eligibility:

The project in supported by the Spanish ministry of science. The application process consist in sending a CV and a proof of your bachelor degree to the formal application page made available. The call is open to EU nationals. There will be ample opportunities to present his/her work at international meetings and conferences. Eligible candidates should apply by sending a complete and up to date CV together with the names and addresses of two academic referees to: Gianni De Fabritiis (gianni.defabritiis at The title of this offer must be clearly stated in any communication.


27th June 2015 CLOSED


N. Stanley, S. Esteban and G. De Fabritiis, Kinetic modulation of a disordered protein domain by phosphorylation, Nat. Commun. 5, 5272 (2014).

S. Doerr and G. De Fabritiis, On-the-fly learning and sampling of ligand binding by high-throughput molecular simulations, J. Chem. Theory Comput. 10 (5), pp 2064–2069(2014).

S. K. Sadiq, F. Noe and G. De Fabritiis, Kinetic characterization of the critical step in HIV-1 protease maturation, PNAS 109 (50) 20449-20454 (2012).

I. Buch, T. Giorgino and G. De Fabritiis,Complete reconstruction of an enzyme-inhibitor binding process by molecular dynamics simulations, PNAS 108, 10184-10189 (2011).

Further references are available at G. De Fabritiis home page