Manual/Adding_Hydrogen_atoms.html at main · openmopac/Manual · GitHub

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<title>Adding hydrogen atoms </title>
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<p><font face="Arial">(<a href="Modeling_proteins.html">Modeling proteins</a>)</font></p>
<h1>&nbsp;</h1>
<h1>Adding Hydrogen Atoms to Protein</h1>
<p class="MsoNormal">
<o:p>Raw PDB files can be hydrogenated by running them as
MOPAC jobs, e.g. running MOPAC with the argument 1A1A.pdb.&nbsp; Because it does
not allow any options this way of hydrogenating a protein is
not normally used.&nbsp; A better
approach is to make up a normal MOPAC data-set that refers to the PDB
file, and run that.&nbsp; This strategy allows options that modify how the
hydrogenation is done.&nbsp; But first, some notes on hydrogenation, to make the
process easier to understand:</o:p></p>
<h2>Initial hydrogenation</h2>
<p class="MsoNormal">The hydrogenation method used in MOPAC has been optimized
for hydrogenating protein systems.<span style="mso-spacerun:yes">&nbsp; </span>
Hydrogen atoms are added by keyword <a href="add-h.html"><tt>ADD-H</tt></a> so as to
neutralize all sites, so, for example, -COO would become -COOH, SO<sub>4</sub>
would become H<sub>2</sub>SO<sub>4</sub>, and O would become H<sub>2</sub>O.<span style="mso-spacerun:yes">&nbsp;
Only metal atoms, such as K and Ca, are ionized</span></p>
<h2>Ionization and other operations</h2>
<h3>Salt bridges</h3>
<p class="MsoNormal">Many proteins contain salt bridges.<span style="mso-spacerun:yes">&nbsp;
</span>These can be added automatically by keyword <a href="site.html">
SITE=(SALT)</a><span style="mso-spacerun:yes">&nbsp; </span>This identifies all
potential salt bridges and adds and deletes hydrogen atoms, as appropriate.<span style="mso-spacerun:yes">&nbsp;
</span></p>
<h2>Other ionized sites</h2>
<p class="MsoNormal">In individual proteins, some sites are known to be ionized,
for example the Asp residue in the protease catalytic triad.<span style="mso-spacerun:yes">&nbsp;
</span>These sites can be ionized using the simple "chain-letter residue number"
approach.<span style="mso-spacerun:yes">&nbsp; </span>Thus if the triad residue
Asp in chymotrypsin were to be in chain "F" and have residue number 102, then
that site could be ionized using SITE=(F102(-)). </p>
<h3>Incorrect site hydrogenated</h3>
<p class="MsoNormal">Some systems, in particular the imidazole ring in
histidine, have two sites that can be hydrogenated.<span style="mso-spacerun:yes">&nbsp;
</span>If the wrong site is hydrogenated, then problems can occur, for example
if one nitrogen in an imidazole ring forms a hydrogen bond with a nearby
residue, then hydrogenating that site might result in a steric clash.<span style="mso-spacerun:yes">&nbsp;
</span>To correct this, the protonation state of each nitrogen in the imidazole
would need to be changed.<span style="mso-spacerun:yes">&nbsp; </span>This
requires a more specific SITE command of the type:</p>
<p align="center" class="MsoNormal">
SITE("[HIS]222:A.ND1"(0),"[HIS]222:A.NE2"(+))</p>
<p align="center" class="MsoNormal">or</p>
<p align="center" class="MsoNormal">SITE("ND1 HIS A 222"(0)," NE2 HIS A 222"(+))</p>
<p class="MsoNormal">In this system, the original hydrogenation incorrectly put
a proton on ND1 of His222 instead of on NE2.<span style="mso-spacerun:yes">&nbsp;
</span>To correct this, the SITE command re-defines ND1 as being neutral and NE2
as being a cation.<span style="mso-spacerun:yes">&nbsp; </span>When the SITE
command is run, it sees that ND1 is a nitrogen atom in an unsaturated ring
(think pyridine) that has a hydrogen atom attached (think pyridinium).<span style="mso-spacerun:yes">&nbsp;
</span>Removal of that hydrogen atom would neutralize the charge.<span style="mso-spacerun:yes">&nbsp;
</span>Similarly defining NE2 as being a cation would result in a hydrogen atom
being added to that atom.</p>
<p class="MsoNormal">These commands can be combined to form a single command
that corrects all the faults in the original hydrogenation, for example:</p>
<p align="center" class="MsoNormal">
SITE(SALT,"[HIS]222:A.ND1"(0),"[HIS]222:A.NE2"(+),F102(-))</p>
<p class="MsoNormal">&nbsp;</p>
<p class="MsoNormal"><o:p>&nbsp;</o:p></p>
<p class="MsoNormal"><o:p>&nbsp;</o:p></p>
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