<s>
The	O
hybrid	O
QM/MM	B-Algorithm
(	O
quantum	O
mechanics/molecular	O
mechanics	O
)	O
approach	O
is	O
a	O
molecular	O
simulation	O
method	O
that	O
combines	O
the	O
strengths	O
of	O
ab	O
initio	O
QM	O
calculations	O
(	O
accuracy	O
)	O
and	O
MM	O
(	O
speed	O
)	O
approaches	O
,	O
thus	O
allowing	O
for	O
the	O
study	O
of	O
chemical	O
processes	O
in	O
solution	O
and	O
in	O
proteins	O
.	O
</s>
<s>
The	O
QM/MM	B-Algorithm
approach	O
was	O
introduced	O
in	O
the	O
1976	O
paper	O
of	O
Warshel	O
and	O
Levitt	O
.	O
</s>
<s>
An	O
important	O
advantage	O
of	O
QM/MM	B-Algorithm
methods	O
is	O
their	O
efficiency	O
.	O
</s>
<s>
The	O
third	O
term	O
accounts	O
for	O
dispersion	O
interactions	O
across	O
the	O
QM/MM	B-Algorithm
boundary	O
.	O
</s>
<s>
Evaluating	O
the	O
charge-charge	O
term	O
in	O
the	O
QM/MM	B-Algorithm
interaction	O
equation	O
given	O
previously	O
can	O
be	O
very	O
computationally	O
expensive	O
(	O
consider	O
the	O
number	O
of	O
evaluations	O
required	O
a	O
system	O
with	O
106	O
grid	O
points	O
for	O
the	O
electron	O
density	O
of	O
the	O
QM	O
system	O
and	O
104	O
MM	O
atoms	O
)	O
.	O
</s>
<s>
Even	O
though	O
QM/MM	B-Algorithm
methods	O
are	O
often	O
very	O
efficient	O
,	O
they	O
are	O
still	O
rather	O
tricky	O
to	O
handle	O
.	O
</s>
<s>
In	O
systems	O
where	O
the	O
QM/MM	B-Algorithm
boundary	O
cuts	O
a	O
bond	O
three	O
issues	O
must	O
be	O
dealt	O
with	O
.	O
</s>
