Welcome to the Carme Rovira group web site.  

Many fundamental biological processes, such as all enzymatic reactions and some ligand-protein interactions, involve mechanisms in which chemical bonds are formed and/or broken, as well as large electronic reorganization. For instance, when oxygen binds to the active center of hemoglobin, the heme prosthetic group  changes from a quintuplet spin state to a singlet state whose electron distribution is still debated.  At the same time, a covalent bond between the oxygen molecule and the heme iron atom develops. Our research is focused on computational simulation of biological processes that involve large electronic changes from an atomistic point of view, using molecular dynamics techniques. Our main tool is ab initio molecular dynamics, in particular the Car-Parrinello method (CPMD), combined with enhanced sampling techniques such as metadynamics and umbrella sampling, to simulate rare events. We also use classical molecular dynamics (based on force-fields) and hybrid quantum mechanics/molecular mechanics (QM/MM) methods.  Most projects are being performed in collaboration with experimental groups of biochemistry, molecular biology and structural biology.

Currently our research focuses on:   
  • Enzymatic synthesis and degradation of carbohydrates (PhD position available!!!)
  • Catalase and peroxidase catalytic mechanisms.
  • Gold clusters and nanoparticles and their interaction with proteins.
Recent representative publications

J. Iglesias-Fernández, S. M. Hancock, S. S. Lee, M. Khan, J. Kirkpatrick, N. J. Oldham, K. McAuley, A. Fordham-Skelton, C. Rovira*, B. G. Davis*. “A Front-Face ‘SNi synthase’ engineered from a retaining ‘double-SN2’hydrolase”. Nature Chemical Biology, 13, 874–881 (2017).

V. Rojas-Cervellera, L. Raich, J. Akola,
C. Rovira
*. The molecular mechanism of the ligand exchange reaction of an antibody against a glutathione-coated gold cluster”. Nanoscale, 9, 3121-3127 (2017).

Y. Jin, M. Petricevic, A. John, L. Raich, H. Jenkins, L. Portela De Souza, F. Cuskin, H. J. Gilbert, C. Rovira
, E. D. Goddard-Borger, S. J. Williams, G. J. Davies. “A β-mannannase with a lysozyme fold and a novel molecular catalytic mechanism”. ACS Cent. Sci., 2, 896–903 (2016).

L. Raich, V. Borodkin, W. Fang, J. Castro-López, D. van Aalten, R. Hurtado-Guerrero, C. Rovira. A trapped covalent intermediate of a glycoside hydrolase on the pathwayto transglycosylation. Insights from experiments and quantum mechanics/molecular mechanics simulations. J. Am. Chem. Soc., 138, 3325−3332 (2016).

Ardèvol, C. Rovira. “Reaction mechanisms incarbohydrate-active enzymes: glycosyl hydrolases and glycosyltransferases.Insights from ab initio QM/MM molecular dynamics simulations.” J. Am. Chem. Soc. 137, 7528-7547 (2015). Perspective article. JACS Spotlight.

P. C. Loewen, X. Carpena, P. Vidossich, I. Fita, C. Rovira. “An ionizable triptophane residue impartscatalase activity to a peroxidase core”. 
J. Am. Chem. Soc. 136, 7249−7252 (2014). JACS Spotlight.

J. Thompson, G. Speciale, J. Iglesias-Fernández, Z. Hakki, T. Belz, A. Cartmell, R. J. Spears, E. Chandler,  J. Stepper, H. J. Gilbert, C. Rovira, S. J. Williams, G. J. Davies. “Evidence for a boatconformation at the transition state of GH76 a-1,6-mannanases; key enzymes inbacterial and fungal mannoprotein metabolism”. Angew. Chem. Int. Ed. 54, 5378-5382 (2015).

E. Lira-Navarrete, M. de las Rivas, I. Compañón, M. C. Pallarés, Y. Kong, J. Iglesias-Fernández, G. J. L. Bernardes, J. M. Peregrina, C. Rovira, P. Bernadó, P. Bruscolini, H. Clausen, A. Lostao, F. Corzana, R. Hurtado-Guerrero. “Dynamic interplaybetween catalytic and lectin domains of GalNAc-transferases modulatesprotein O-glycosylation”. Nat. Commun. 6, 6937 (2015).

J. Thompson, J. Dabin, J. Iglesias-Fernández, A. Ardèvol, Z. Dinev, S. J. Williams, O. Bande, A. Siriwardena, C. Moreland, T.-C. Hu, D. K. Smith, H. J. Gilbert, C. Rovira, G. J. Davies. “The reaction coordinateof a bacterial GH47 α-mannosidase: a combined quantum mechanical and structuralapproach”.
Angew. Chem. Int. Ed. 51, 10997-11001 (2012). Editorial VIP.

G. J. Davies, A. Planas, C. Rovira. "Conformational analyses of the reaction coordinate of glycosidases”. Acc. Chem. Res. 45, 308–316 (2012).

Ardèvol, C. Rovira. “The molecularmechanism of enzymatic glycosyl transfer with retention of configuration: evidencefor a short-lived oxocarbenium ion-like species”.
Angew. Chem. Int. Ed. 50, 10897-10901 (2011). Editorial VIP.


The conformational free energy landscape of the mannoimidazole inhibitor (center panel) displays a strong preference for the transition state conformations found in beta-mannanases (Angew. Chem. Int. Ed. 53, 1087, 2014)