Monte Carlo and modified Tanford-Kirkwood results for macromolecular electrostatics calculations

The understanding of electrostatic interactions is an essential aspect of the complex correlation between structure and function of biological macromolecules. It is also important in protein engineering and design. Theoretical studies of such interactions are predominantly done within the framework of Debye-Huckel theory. A classical example is the Tanford-Kirkwood (TK) model. Besides other limitations, this model assumes an infinitesimally small macromolecule concentration. By comparison to Monte Carlo (MC) simulations, it is shown that TK predictions for the shifts in ion binding constants upon addition of salt become less reliable even at moderately macromolecular concentrations. A simple modification based on colloidal literature is suggested to the TK scheme. The modified TK models suggested here satisfactorily predict MC and experimental shifts in the calcium binding constant as a function of protein concentration for the calbindin D-9k mutant and calmodulin.Univ Estadual Paulista, Inst Biociencias Letras & Ciências Extras, Dept Fis, BR-15054000 Sao Jose do Rio Preto, SP, BrazilUniv Estadual Paulista, Fac Ciências, Dept Fis, BR-17033360 Bauru, SP, BrazilUniv São Paulo, Fac Ciências Farmaceut Ribeirao Preto, Dept Fis & Quim, BR-14040903 Ribeirao Preto, SP, BrazilUniv Estadual Paulista, Inst Biociencias Letras & Ciências Extras, Dept Fis, BR-15054000 Sao Jose do Rio Preto, SP, BrazilUniv Estadual Paulista, Fac Ciências, Dept Fis, BR-17033360 Bauru, SP, Brazi

On the complexation of proteins and polyelectrolytes

Both natural and synthetic polyelectrolytes form strong complexes with a variety of proteins. One peculiar phenomenon is that association can take place even when the protein and the polyelectrolyte carry the same charge. This has been interpreted as if the ion-dipole interaction can overcome the repulsive ion-ion interaction. On the basis of Monte Carlo simulations and perturbation theory, we propose a different explanation for the association, namely, charge regulation. We have investigated three different protein-polymer complexes and found that the induced ionization of amino acid residues due to the polyelectrolyte leads to a surprisingly strong attractive interaction between the protein and the polymer. The extra attraction from this charge-induced charge interaction can be several kT and is for the three cases studied here, lysozyme, alpha-lactalbumin, and beta-lactoglobulin, of the same magnitude or stronger than the ion-dipole interaction. The magnitude of the induced charge is governed by a response function, the protein charge capacitance - (2). This fluctuation term can easily be calculated in a simulation or measured in a titration experiment

Application of a new reverse Monte Carlo algorithm to polyatomic molecular systems. I. Liquid water

Using a new reverse Monte Carlo algorithm, we present simulations that reproduce very well several structural and thermodynamic properties of liquid water. Both Monte Carlo, molecular dynamics simulations and experimental radial distribution functions used as input are accurately reproduced using a small number of molecules and no external constraints. Ad hoc energy and hydrogen bond analysis show the physical consistency and limitations of the generated RMC configurations. (C) 2001 American Institute of Physics