<s>
Lead	B-Application
Finder	I-Application
software	O
is	O
a	O
computational	O
chemistry	O
application	O
for	O
modeling	O
protein-ligand	O
interactions	O
.	O
</s>
<s>
Lead	B-Application
Finder	I-Application
software	O
is	O
an	O
integrated	O
solution	O
for	O
simulating	O
structure	O
and	O
binding	O
affinity	O
of	O
protein-ligand	O
complexes	O
.	O
</s>
<s>
Original	O
docking	O
algorithm	O
provides	O
a	O
fast	O
rate	O
of	O
calculations	O
,	O
which	O
can	O
be	O
easily	O
adjusted	O
from	O
more	O
rapid	O
(	O
for	O
virtual	O
screening	O
applications	O
)	O
to	O
slightly	O
more	O
slow	O
and	O
robust	O
,	O
while	O
unique	O
scoring	O
function	O
implemented	O
in	O
Lead	B-Application
Finder	I-Application
provides	O
unsurpassed	O
accuracy	O
of	O
calculations	O
.	O
</s>
<s>
Lead	B-Application
Finder	I-Application
is	O
intended	O
to	O
meet	O
the	O
requirements	O
of	O
computational	O
and	O
medicinal	O
chemists	O
involved	O
in	O
drug	O
discovery	O
,	O
pharmacologists	O
and	O
toxicologists	O
involved	O
in	O
the	O
evaluation	O
of	O
ADMET	O
properties	O
in	O
silico	O
,	O
and	O
biochemists	O
and	O
enzymologists	O
working	O
on	O
modeling	O
protein-ligand	O
interactions	O
,	O
enzyme	O
specificity	O
and	O
rational	O
enzyme	O
design	O
.	O
</s>
<s>
Efficiency	O
of	O
ligand	O
docking	O
and	O
binding	O
energy	O
estimations	O
achieved	O
by	O
Lead	B-Application
Finder	I-Application
are	O
due	O
to	O
docking	O
algorithm	O
and	O
extra	O
precision	O
representation	O
of	O
protein-ligand	O
interactions	O
.	O
</s>
<s>
To	O
tackle	O
this	O
computationally	O
challenging	O
problem	O
,	O
Lead	B-Application
Finder	I-Application
applies	O
a	O
unique	O
approach	O
combining	O
genetic	B-Algorithm
algorithm	I-Algorithm
search	O
,	O
local	O
optimization	O
procedures	O
,	O
and	O
a	O
smart	O
exploitation	O
of	O
the	O
knowledge	O
generated	O
during	O
the	O
search	O
run	O
.	O
</s>
<s>
Rational	O
combination	O
of	O
different	O
optimization	O
strategies	O
makes	O
Lead	B-Application
Finder	I-Application
efficient	O
in	O
terms	O
of	O
coarse	O
sampling	O
of	O
ligand	O
's	O
phase	O
space	O
and	O
refinement	O
of	O
promising	O
solutions	O
.	O
</s>
<s>
Extra	O
precise	O
representation	O
of	O
protein-ligand	O
interactions	O
implemented	O
in	O
Lead	B-Application
Finder	I-Application
scoring	O
function	O
is	O
the	O
second	O
(	O
in	O
addition	O
to	O
docking	O
algorithm	O
)	O
component	O
of	O
successful	O
ligand	O
docking	O
.	O
</s>
<s>
Lead	B-Application
Finder	I-Application
scoring	O
function	O
is	O
based	O
on	O
a	O
semi-empiric	O
molecular	O
mechanical	O
functional	O
,	O
which	O
explicitly	O
accounts	O
for	O
different	O
types	O
of	O
molecular	O
interactions	O
.	O
</s>
<s>
For	O
these	O
reasons	O
,	O
three	O
distinct	O
types	O
of	O
scoring	O
functions	O
based	O
on	O
the	O
same	O
set	O
of	O
energy	O
contributions	O
but	O
different	O
sets	O
of	O
energy-scaling	O
coefficients	O
are	O
used	O
by	O
Lead	B-Application
Finder	I-Application
.	O
</s>
<s>
The	O
ability	O
of	O
Lead	B-Application
Finder	I-Application
to	O
estimate	O
free	O
energy	O
of	O
protein-ligand	O
binding	O
was	O
benchmarked	O
against	O
the	O
set	O
of	O
330	O
diverse	O
protein-ligand	O
complexes	O
,	O
which	O
is	O
currently	O
the	O
most	O
extensive	O
benchmarking	O
study	O
of	O
such	O
kind	O
.	O
</s>
<s>
Lead	B-Application
Finder	I-Application
demonstrated	O
unique	O
precision	O
of	O
binding	O
energy	O
prediction	O
(	O
RMSD	O
=	O
1.5	O
kcal/mol	O
)	O
combined	O
with	O
high	O
speed	O
of	O
calculations	O
(	O
less	O
than	O
one	O
second	O
per	O
compound	O
on	O
average	O
)	O
.	O
</s>
