Docking of calcium ions in proteins with flexible side chains and deformable backbones

A method of docking Ca2+ ions in proteins with flexible side chains and deformable backbones is proposed. The energy was calculated with the AMBER force field, implicit solvent, and solvent exposure-dependent and distance-dependent dielectric function. Starting structures were generated with Ca2+ coordinates and side-chain torsions sampled in 1000 Å3 cubes centered at the experimental Ca2+ positions. The energy was Monte Carlo-minimized. The method was tested on fourteen Ca2+-binding sites. For twelve Ca2+-binding sites the root mean square (RMS) deviation of the apparent global minimum from the experimental structure was below 1.3 and 1.7 Å for Ca2+ ions and side-chain heavy atoms, respectively. Energies of multiple local minima correlate with the RMS deviations from the X-ray structures. Two Ca2+-binding sites at the surface of proteinase K were not predicted, because of underestimation of Ca2+ hydration energy by the implicit-solvent method.