Exploring protein native states and large‐scale conformational changes with a modified generalized born model

Implicit solvation models provide, for many applications, a reasonably accurate and computationally effective way to describe the electrostatics of aqueous solvation. Here, a popular analytical Generalized Born (GB) solvation model is modified to improve its accuracy in calculating the solvent polarization part of free energy changes in large-scale conformational transitions, such as protein folding. In contrast to an earlier GB model (implemented in the AMBER-6 program), the improved version does not overstabilize the native structures relative to the finite-difference Poisson-Boltzmann continuum treatment. In addition to improving the energy balance between folded and unfolded conformers, the algorithm…