Re: how can I know which type HIS belong to?(HSD,HSE,HSP)

From: Fangqiang Zhu (fzhu_at_ks.uiuc.edu)
Date: Sat Nov 29 2003 - 00:22:03 CST

Hi,

Unfortunately, there's not a really accurate and easy solution for this
problem, as far as I can tell.

In practice, many people simply assume that all of the histidines in
their protein are HSD or HSE, and hope that the position of the
protonated nitrogen is not important for their result.

However, if you want to be more careful, or you know that certain
histidines are very critical for the stability or the function of your
protein, you might want to think more about them. By visually
inspecting the histidines and their nearby residues in the crystal
structure, you might be able to tell whether HSD or HSE would make
more sense, e.g., if one state can form a nice hydrogen bond network
with other residues while the other state can't. It's also likely that
you may get some clues from experiments. If the protonation state
of a histidine is extremely important for your simulation, you can
even generate two structures, one with HSD and the other with
HSE, then do simulations on both of them, and then judge from the
trajectories which state is more reasonable.

In any case, this is not an easy business, and everyone has to make
a (more or less random) decision by himself...

Zhu, Fangqiang

yxiong_at_mail.ccnu.edu.cn wrote:

> Dear sir,
> In the tutorial of NAMD program, there is the following advice:
> ----------------------------------------------------------------------
> Histidine Residues. Of the 20 amino acids, histidine is the only
> one which ionizes within the physiological pH range ( ˘ 7.4). This
> effect is characterized by the pKa of the amino acid side chain. For
> histidine, the value is 6.04. This leads to the possiblilty of different
> protonation states for histidine residues in a protein, and makes the
> consideration of the proper state important in MD simulations. The
> viable states are one in which the  nitrogen of histidine is protonated
> (listed with residue name ¡°HSD¡± in the topology file), one in which
> the  nitrogen of histidine is protonated (¡°HSE¡±), and one in which
> both nitrogens are protonated (¡°HSP¡±).
> -----------------------------------------------------------------------
> Since the H atoms are not available from the original pdb file, how can I know
> which type HIS belong to?
> Thanks!

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