Protein control of iron-sulfur cluster redox potentials.

Experimental pKa Values of Buried Residues: Analysis with Continuum Methods and Role of Water Penetration

“…Self-consistent calculation of pK a values of surface and buried groups using a single value of ⑀ in is impossible with semi-macroscopic methods unless protein flexibility is taken into account explicitly. When conformational relaxation is treated explicitly, low ⑀ in can yield reasonable results (Langsetmo et al, 1991;Antosiewicz et al, 1994Antosiewicz et al, , 1996You and Bashford, 1995;Alexov and Gunner, 1997;Zhou and Vijayakumar, 1997;Rabenstein et al, 1998;van Vlijmen et al, 1998;Havranek and Harbury, 1999;Scharnagl et al, 1999;Ullmann and Knapp, 1999), especially when the neutral and the ionized states of the group of interest are treated separately to capture contributions by the relaxation of local dipoles upon ionization (Langen et al, 1992;Yang et al, 1993;Alexov and Gunner, 1997;Sham et al, 1997;Zhou and Vijayakumar, 1997;Rabenstein and Knapp, 2001). In microscopic methods, such as the protein dipole-Langevin dipole (PDLD) method developed by Warshel and co-workers, the relaxation of protein dipoles has always been included explicitly (Warshel and Russell, 1984).…”

“…To evaluate contributions by buried water molecules to the pK a value of Glu-66, a continuum calculation was performed in which some of the internal water molecules were treated explicitly, as done previously by others (Langen et al, 1992;Yang et al, 1993;Gibas and Subramaniam, 1996;Alexov and Gunner, 1999;Schutz and Warshel, 2001). Only four waters were treated explicitly, the two that are hydrogen bonded directly to the carboxyl oxygen atoms of Glu-66, and the two that connect these with bulk water (Dwyer et al, 2000).…”

“…The problem can be avoided if, instead of using a single conformation in the calculations, the microscopic reorganization of the specific environments around the charges is accounted for explicitly. This can be done by the linear response approximation formulation of Warshel and coworkers, which requires averaging over the charge and uncharged configurations (Langen et al, 1992), and by a similar treatment in the more recent methods (Alexov and Gunner, 1997;van Vlijmen et al, 1998;Schutz and Warshel, 2001). These problems are also avoided in the method developed by Mehler and co-workers, which is based on the use of screened coulombic potentials coupled with a hydrophobicity parameter to account for variations in local microenvironments of ionizable groups (Mehler and Guarnieri, 1999).…”

High Apparent Dielectric Constant Inside a Protein Reflects Structural Reorganization Coupled to the Ionization of an Internal Asp

“…The presence of these internal water molecules led to the hypothesis that water penetration is the source of the high polarizability reported by internal ionizable groups in SNase. This has been considered previously in computational studies (8)(9)(10).…”

Calculation of Electron Transfer Reorganization Energies Using the Finite Difference Poisson-Boltzmann Model

“…A linear dielectric model for the solvent has also been combined successfully with self-consistent quantum mechanical calculations of for intramolecular electron transfer in small molecules (Liu and Newton, 1995). Linear response models of electrostatics, including those based on numerical solutions to the Poisson-Boltzmann (PB) equation, have also proven to be highly successful for modeling many equilibrium electrostatic properties of proteins, including redox midpoint potentials (Bashford et al, 1988;Churg and Warshel, 1986;Gunner and Honig, 1990;Langen et al, 1992). A key ingredient in this success has been the ability to rapidly and accurately solve the PB equation for essentially any arbitrary charge and dielectric distribution using finite difference (FD) and finite element (FE) methods (Holst and Saied, 1993;Rashin and Namboodiri, 1987;Zauhar and Morgan, 1985).…”