Insight 2 software

All molecular modeling was conducted by Insight II software (Accelrys, San Diego, CA, USA) on a Silicon Graphics Octane workstation. Phenacetin was constructed and minimized using the Insight II/Builder module. Energy minimization and MD simulations were performed by the Insight II/Discover module with the consistent valence force field (CVFF). The parameters for heme containing Fe³⁺ had been described earlier [17 (link),36 (link),37 (link)].

The electrostatic potentials of PH domains were calculated using a finite different solution to the nonlinear Poisson-Boltzmann equation [32 (link)]. The grid was 20 Å larger than the PH molecule containing 123 grid points in the longest dimension. The solute dielectric was set to 2. Solvent accessible surface areas (SASA) were calculated according to the algorithm of Lee and Richards [33 (link)], and a solvent radius of 1.4 Å was used for water. The fractions of residues exposed to solvent were calculated directly from the experimental structures and were subsequently used to generate profiles with the sliding window averaging technique to facilitate comparison to the predicted properties. In the case of NMR structures missing the average structure (1MPH, 1PLS, 1BAK, and 1FHO), the first structure in the entry was used. The detailed interatomic contacts for inositol phosphate to PH domains were investigated with the LIGIN program [34 (link)]. All the other structural analyses were performed with InsightII software of Accelrys, Inc.