Electrostatics: Understanding Biomolecular Solvation

Importance of electrostatics

Chemistry can essentially be described as the science of interactions between electrons and their associated wave functions. As such, electrostatics is at the core of all chemical and subsequently biological processes. Quantifying electrostatic interactions has been the focus of many research efforts in biophysical sciences for at least one century; yet we are still lacking a set of accurate tools for computing the electrostatic properties of biomolecules immersed in a solvent and surrounded with an ion atmosphere that can be used for the analysis of experiments, for the prediction of the stability, dynamics and function of biomolecules. Such tools are a prerequisite for the design of molecular partners or inhibitors, as in drug design. They need to be solidly anchored into the physical principles that govern biomolecular electrostatics and at the same time be accessible to the biomedical community at large, with minimal practical requirements in term of computing needs.

Computing the solvation energy of a biomolecule

Soluble biomolecules adopt their stable conformation in water, and are unfolded in the gas phase. It is therefore essential to account for water in any modeling experiment. Molecular dynamics simulation that include a large number of solvent molecules are the state of the art in this field, but they are inefficient as most of the computing time is spent on updating the position of the water molecule. It should further be noted that it is not always possible to account for the interaction with the solvent explicitly. For example, energy minimization of a system including both a protein and water molecules does not account for the entropy of water, which would behave like ice with respect to the protein. An alternative approach takes the effect of the solvent implicitly into account. In such an implicit solvent model, the effects of water is included in an effective solvation potential, W = W_elec + W_np, in which the first term accounts for the molecule-solvent electrostatics polarization, and the second for the molecule-solvent van der Waals interactions and for the formation of a cavity in the solvent.

I have worked with Prof. Edelsbrunner on computing the second term involved in the implicit solvent models described above (see Shapes section). In parallel, I have recently developed in collaboration with Dr Marc Delarue, Institut Pasteur, France, and Dr Henri Orland, CEA, Saclay, an extension to the Poisson Boltzmann formalism, namely the Dipolar Poisson-Boltzmann Langevin (DPBL) model that circumvents the limits of the former as it allows for non uniform dielectric property of the solvent and accounts for the sizes of ions. We have extended this formalism to account for vdW interactions between the water dipoles and we have developed a fast and accurate numerical solver for the corresponding non linear partial differential equations, AquaSol .

DNA solvation.

Ion solvation.