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Dr Edina Rosta


Reader in Computational Chemistry


Tel: +44 (0)20 7848 7334

Address: Department of Chemistry            King's College London                                  Room 113, Britannia House                             7 Trinity Street                                                 London SE1 1DB 

Research Interests and Research Projects

The formation and cleavage of phosphate bonds are essential in most biological processes including reproduction, protein synthesis, signal transduction, energy storage, and transfer. We use computational methods to help reveal the molecular mechanisms of how enzymes can achieve both a high efficiency and specificity catalysing phosphate hydrolysis and transfer reactions.

We developed quantum-classical QM/MM simulation techniques combining Hamiltonian replica exchange with the finite temperature string method. These methods accurately model bond breaking and forming using ab initio calculations and also provide an enhanced sampling of protein conformations. We develop further novel computational methods that are applicable to accurately estimate enzyme activities in biomolecular complexes.

Metal ions are required for many enzymes and ribozymes to function. One- and two-metal ion catalysis are ubiquitous mechanisms employing metal ions in the centre of the active sites. Examples include kinases and phosphatases involved in signalling, polymerases and RNases involved in gene expression, and ATPases involved in molecular machines. We study the roles of metal ions in the catalytic mechanism, in particular, the changes in metal ion coordination and their roles in proton transfer processes coupled to the chemical step. Our research is strongly motivated by the potential applications to designing new drugs for diseases such as cancer and AIDS, by exploiting the possibility of direct binding between inhibitor and metal ion.

In addition to atomistic molecular simulations, high-level models of interacting biomolecules offer a complementary, top-down approach to integrate detailed atomistic information with network models of activities and interaction patterns of biomolecular complexes. We aim to use kinetic network models to characterise the complex protein-protein interactions that drive signaling pathways by determining kinase activities. Recently we applied kinetic network models to analyse the efficiency of enhanced sampling methods for biomolecular simulations. We proposed a new kinetic network model to quantitatively describe replica exchange processes. Using this model, we obtained an analytic efficiency expression for both simulated tempering and replica exchange simulation methods. Our long term aim is to use the developed network models of signaling pathways together with the high resolution QM/MM simulation results to design better initial drug screening strategies for specific inhibitors of kinases with cancer causing mutations.

Dr Rosta is a member of the Thomas Young Centre.

More details can be found here:

Research Projects:

  • QM/MM simulations of metal ion catalysed phosphate hydrolysis and transfer.
  • Kinetic network models of molecular signalling pathways.
  • Ab initio method development exploring substituent effects in Marcus theory of electron transfer

Dr Rosta's Research Portal 

Research Group: Rosta

Edina Rosta's group looks at the formation and cleavage of phosphate bonds, which are essential to most biological processes including reproduction, protein synthesis, signal transduction, energy storage, and transfer. The group uses computational methods to reveal the molecular mechanisms of how enzymes can achieve both high efficiency and specificity in catalysing phosphate hydrolysis and transfer reactions.

Rosta Research Page 

Selected Publications
  • E. Rosta, W. Yang and G. Hummer, "Calcium inhibition of Ribonuclease H1 two-metal ion catalysis" Journal of the American Chemical Society, 2014 (DOI: 10.1021/ja411408x)
  • A. Ganguy, P. Thaplyal, E. Rosta, P. Bevilaqua, and S. Hammes-Schiffer, “Quantum Mechanical/Molecular Mechanical Free Energy Simulations of the Self-Cleavage Reaction in the Hepatitis Delta Virus Ribozyme.", Journal of the American Chemical Society, 2014, 136  (4), 1483-1496
  • T. Pesnot, L. M. Tedaldi, P. G. Jambrina, E. Rosta and G. K. Wagner, “Exploring the role of the 5-substituent for the intrinsic fluorescence of 5-aryl and 5-heteroaryl uracil nucleotides: a systematic study” Organic & Biomolecular Chemistry, 2013, 11, 6357-6371
  • O. Barabás, V. Németh, A. Bodor, A. Perczel, E. Rosta, Z. Kele, I. Zagyva, Z. Szabadka, V. I. Grolmusz, M. Wilmanns and B. G. Vértessy, “Catalytic mechanism of α-phosphate attack in dUTPase is revealed by X-ray crystallographic snapshots of distinct intermediates, 31P-NMR spectroscopy and reaction path modelling” Nucleic Acids Research, 2013,41 (22), 10542-10555
  • I. Lans, M. Medina, E. Rosta, G. Hummer, M. Garcia-Viloca, J. M. Lluch, and A. Gonzalez-Lafont, “Theoretical study of the mechanism of the hydride transfer between Ferredoxin NADP+ reductase and NADP+. The role of Tyr303.", Journal of the American Chemical Society, 2012, 134  (50), 20544-20553
  • E. Rosta and A. Warshel, "Origin of Linear Free Energy Relationships: Exploring the Nature of the Off-Diagonal Coupling Elements in S(N)2 Reactions"  Journal of Chemical Theory and Computation, Vol. 8, 3574, 2012
  • E. Rosta, M. Nowotny, W. Yang and G. Hummer, “Catalytic Mechanism of RNA Backbone Cleavage by Ribonuclease H from QM/MM Simulations”,Journal of the American Chemical Society, Vol. 133, 8934, 2011
  • E. Rosta and G. Hummer, “Error and Efficiency of Simulated TemperingSimulations”, Journal of Chemical Physics, Vol. 131, 034102, 2010
  • E. Rosta and G. Hummer, “Error and Efficiency of Replica Exchange Molecular Dynamics Simulations”, Journal of Chemical Physics , Vol. 131, 165102, 2009
  • E. Rosta, N-V. Buchete and G. Hummer, “Thermostat artifacts in replica exchange molecular dynamics simulations: distortions of the protein folding equilibrium”, Journal of Chemical Theory and Computation, Vol. 5, 1393,2009
  • E. Rosta, H. L. Woodcock, Y. Shao, B. Brooks and G. Hummer, “Artificial reaction coordinate “tunneling” in free energy calculations: the catalytic reaction of Ribonuclease H”, Journal of Computational Chemistry, Vol. 96, 573a, 2009
  • E. Rosta, M. Haranczyk, Z. T. Chu and A. Warshel, “Accelerating QM/MM Free Energy Calculations: Representing the Surroundings by an Updated Mean Charge Distribution”, Journal of Physical Chemistry B, Vol. 112, 5680,2008
  • E. Rosta, S. L. Kamerlin and A. Warshel, “On the Interpretation of the Observed Linear Free Energy Relationship in Phosphate Hydrolysis: A Thorough Computational Study of Phosphate Diester Hydrolysis in Solution”, Biochemistry, Vol. 47, 3725, 2008


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