Why H++ ? Structure and function of macromolecules depend critically on
the ionization (protonation) states ( pK ) of their acidic and basic groups.
affinities of proteins for ligands depend
on the pKs of the groups in or near the binding sites;
groups with unusual pKs are often found in active sites of enzymes. Atomistic
simulations of macromolecules require specification of the protonation state of
the titratable groups.
Whether or not a given group is protonated depends, in a non-trivial way, on the position of the group within the molecule as well on the characteristics of the surrounding solvent such as its pH and ionic strength.
Experimental determination (usually by NMR) of protonation equilibria is expensive and often can not be performed for every group of interest.
The most common source of high resolution structures -- X-ray crystallography -- normally does not provide positions of the hydrogen atoms.
The gap is bridged by theoretical methods that predict protonation states (pK) of ionizable groups within the macromolecule based on its
atomic resolution structure. This web site provides access to a set of
tools that automate this process.