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Methodological developments in continuum electrostatic methods

Methodological developments in continuum electrostatic methods

The treatment of electrostatic interactions in simulation methodologies is of fundamental importance to understand protein structure and function. Phenomena like redox reactions and the protonation behaviour of proteins can be understood comparatively using electrostatic methods that account for the solvation part of these reactions. However, molecular electrostatics is one of the most difficult problems to deal with using modelling methods. For this reason, and since the biological problems we want to tread demand it, we are actively in developing methodologies to improve the treatment of electrostatic interactions. Most of this work is done using continuum electrostatic techniques. We develop work is on the multi-state treatment of redox and protonation equilibria in proteins, using Metropolis Monte Carlo methods. We developed, for the first time, a methodology to threat the joint equilibria of protons and electrons in proteins, a necessity when dealing with coupling phenonema in redox proteins. Quite recently, we developed a methodology to treat the equilibria between proton tautomeric forms of protonatable groups, a methodology that can be extended to any group having protons with conformational freedom, allowing the treatment of water molecules in a multiconfigurational manner. These developments resulted in several improvements in prediction accuracy, and allowed us to study new classes of phenomena.

Two dimensional (pH and E) redox titration of cytochrome c3(Baptista et al. (1999), Biophys.J., 76, 2978-2998).

Relevant publications

  • Baptista, A.M., Martel, P.J., Soares, C.M. (1999) "Simulation of electron-proton coupling with a Monte Carlo method: application to cytochrome c3 using continuum electrostatics", Biophys.J., 76, 2978-2998.
  • Baptista, A.M., Soares, C.M. (2000) "Some theoretical and computational aspects of the inclusion of proton isomerism in the protonation equilibrium of proteins", J. Phys. Chem.B, 105, 293-309
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