Je. Nielsen et G. Vriend, Optimizing the hydrogen-bond network in Poisson-Boltzmann equation-based pK(a) calculations, PROTEINS, 43(4), 2001, pp. 403-412
pK(a) calculation methods that are based on finite difference solutions to
the Poisson-Boltzmann equation (FDPB) require that energy calculations be p
erformed for a large number of different protonation states of the protein.
Normally, the differences between these protonation states are modeled by
changing the charges on a few atoms, sometimes the differences are modeled
by adding or removing hydrogens, and in a few cases the positions of these
hydrogens are optimized locally. We present an FDPB-based pK(a) calculation
method in which the hydrogen-bond network is globally optimized for every
single protonation state used. This global optimization gives a significant
improvement in the accuracy of calculated pK(a) values, especially for bur
ied residues. It is also shown that large errors in calculated pK(a) values
are often due to structural artifacts induced by crystal packing. Optimiza
tion of the force fields and parameters used in pK(a) calculations should t
herefore be performed with X-ray structures that are corrected for crystal
artifacts. Proteins 2001;43:403-412. (C) 2001 Wiley-Liss, Inc.