The Institute of Theoretical and Computational Chemistry of the University of Barcelona (IQTCUB) offers two fellowships to students who are finishing their undergraduate university studies and are interested in pursuing an official master’s degree at the UB and at the same time in collaborating on a research project in the IQTC, in the frame of the Màster+ UB program. VISIT https://www.iqtc.ub.edu/education-outreach/fellowships/ for more information.

The following projects are available at the IQTC:

Multiscale QM/MM simulation of the optical properties of ligands (Prof. Carles Curutchet)

The project will focus on the simulation of the absorption and emission properties of a set of small ligands with tailored properties to perform excitation transfer processes with Trp residues in protein-ligand complexes. The project will combine ground state and excited state adiabatic BOMD QM/MM simulations with polarizable TD-DFT QM/MM calculations of excited-state properties.

Structural basis of the selective direct activation of AMPK: β1- versus β2-isoform dependent complexes (Dr Carolina Estarellas)

AMPK is a key energy sensor regulating cell metabolism in response to energy supply and demand. AMPK is a heterotrimer formed by alpha, beta and gamma subunits. The evolutionary adaptation of AMPK to different tissues is accomplished through the expression of distinct isoforms that can form up to 12 complexes, which exhibit notable differences in the sensitivity to allosteric activators. To shed light on the allosteric regulation of this energy sensor, in this project we will assess the structural and dynamical properties of isoform-dependent AMPK complexes formed with small molecules that could act as direct activators, where in some cases activates specifically one of the isoforms, while in other cases these ligands could act as a pan-activators or even inhibitors. So, which are the molecular factors that determine these differences?
We will run molecular dynamic simulations of several complexes formed by alpha-beta AMPK subunits, and the full heterotrimer with different ligands in order to dissect the mechanical response leading to active-like enzyme conformations through the analysis of interaction networks between structural domains.

Effect of macromolecular crowding in enzymatic processes of cellular metabolism (Prof. Francesc Mas)

A development and application of Langevin and Brownian dynamics simulation codes will be performed to study the diffusion and enzymatic reaction in crowded or agglomerated media (high concentration of particles) that mimic the cellular interior. The cytosol is a very dense particle medium, with a high concentration of macromolecules that by non-specific interactions infers an effect on the properties diffusive and reactive of macromolecules.
In this work, the EspresoMD package will first be used for this purpose to study realistic conditions that simulate the cell interior. The program generates stochastically the motion of macromolecules by Langeving or Brownian dynamics algorithm and the enzymatic reaction is considered from random Monte Carlo criteria linking the reaction probabilities with the reaction constants.
The simulations will allow the quantitative analysis of the effect of the volume excluded by some systems enzymes that follow the Michaelis-Menten mechanism.

Unveiling molecular mechanisms of glycoprocessing enzymes using computer simulation. (Prof. Carme Rovira)

It is nowadays known that diseases such as the common flu, diabetes, asthma, some types of cancer and lysosomal storage diseases are related to malfunctioning of specific glycoprocessing enzymes. Finding molecules that selectively block specific enzymes and developing therapeutic probes for diagnosis are very active fields of research. In the last years, our group has developed efficient approaches to unveil the molecular mechanisms of glycoprocessing enzymes by means of quantum mechanics/molecular mechanics (QM/MM) and molecular dynamics simulations. In this project, we aim to use these methods to identify the conformational itinerary and reaction mechanisms of glycosyltransferase enzymes involved in two of the most common lysosomal storage diseases, Gaucher and Fabry disease, as well as and design inhibitors able to block the enzyme’s activities. Further information: http://www.ub.edu/sqpbio

Artificial Intelligence as a tool to increase the predictive power of scoring functions  (Prof. Jaime Rubio Martínez)

Artificial Intelligence (AI) is an emergent research field that is being applied to many aspects of drug design. This project will focus on the application of AI to the obtention of a scoring function that includes the solvation effect in the binding process. We expect to introduce this effect not only in the docking process but also along with a molecular dynamic simulation.

Deadline: 12/07/2021