Electronic and Atomic Protein Modelling


The theoretical study of functional proteomics requires a complete understanding of the different times scales in biochemical processes. The fast motions, often involving a chemical reaction, might require a time-dependent quantum mechanical description of the active site. The slow motions, responsible for conformational changes, require the description of the biological environment (such as protein-protein interaction, solvent, etc.) and various physical properties (such as temperature, pressure). An accurate description of these different time scales bridges the gap between theoretical and experimental studies.

Our group focuses on the theoretical modeling of these different time scales in order to achieve atomic (and electronic) detailed information of protein biochemistry and biophysics.


Guallar, Victor (ICREA Research Professor)


Explore the chemical and physical responses to local and global configuration changes, which may be achieved by coupling a quantum-mechanical description of the reactive process with advanced sampling techniques. For this purpose, several simulation protocols and algorithms, which combine optimized sampling techniques with hybrid QM/MM methods and semiclassical dynamics corrections, are being studied. The objectives are centered in two main areas.

  1. First, we place particular on the application of such methods, with emphasis on protein-substrate interactions and long time protein conformational dynamics. Current application studies include electron transfer and catalysis mechanism studies on heme proteins, fatty acid migration on fatty acid binding protein, Abr-BCL leukemia inhibitors mechanism, etc.
  2. The second area involves the development of new methodological components, focusing on obtaining long time protein dynamics by means of a kinetic Monte Carlo scheme. This area involves mainly the continuous development of our own code PELE.

These two areas provide different venues for students/researchers to explore, based on their strengths and interests. Inquire Prof. Guallar about lab openings!.


Orbital PictureElectron transfer in proteins. Using mixed quantum mechanics/molecular mechanics techniques (QM/MM) we have developed algorithms capable of tracking the electron transfer pathway and its rate. By using the QM/MM e-pathway you can track long range electron transfer pathways. Applications to specific systems include: Cytochrome C Oxidase, protein-protein electron transfer (CCp-CcP), etc. 

QM/MM biochemical studies: Cytochrome C Oxidase and  globin proteins. In collaboration with Prof. Dennis Rousseau and Prof. Syun-Ru Yeh (AECOM), we are investigating the oxygen reduction by Cytochrome C Oxidase. Together with Tom Spiro (Washington University) we are working on the human hemoglobin allosteric mechanism.

Biochemistry and evolution studies on oxidases. In collaboration with Prof. Angel Martinez (CIB-CSIC) and Miguel Alcalde (ICP-CSIC) we are working on different oxidases molecular mechanism. In vitro and in silico mutational studies are being introduced to enhance enzymatic activity.     

Protein Energy Landscape Exploration (PELE). Our code PELE allows mapping (quick and accurately) protein-ligand dynamics. Want to see how a ligand binds into your target, induced fits effect? It is just a click away (and free): https://pele.bsc.es/

Application in drug discovery. Using PELE, and in collaboration with several labs and pharma companies, we are conducting rational drug design. Systems under study include: mTOR, VEGF, MCL, etc.