Solva&on


The
term
“solva&on”
refers
to
the
interac&on
of
a
solute
with
the
solvent
molecules

surrounding
it



There
are
several
approaches
to
modeling
solvent.



Ques&ons
to
consider:



How
detailed
does
the
solvent
(water)
model
need
to
be?


Explicit
or
Implicit


Rigid
or
Flexible


Polarizable
or
Non‐polarizable


Classical
or
Quantum
Mechanical



Is
the
solvent
model
compa&ble
with
the
solute
model


What
does
it
mean
to
be
“compa&ble”?



Is
dynamics
important?

 Force
Field
Poten&al
Func&ons


The
poten&al
func&ons
may
be
divided
into
bonded
terms,
which
give
the
energy

contained
in
the
internal
degrees
of
freedom,
and
non‐bonded
terms,
which

describe
interac7ons
between
molecules.


E pot = ∑V + ∑Vθ + ∑Vτ + ∑V

r vanderWaals + ∑Velectrostatics
bonds angles torsions atoms atoms

Poten7als
between
bonded
atoms
 Poten7als
between
non‐bonded
atoms

=
zero
for
most
water
models


Total
poten7al
Energy,
Epot
or
Vtot

 Electrosta&cs
and
Solva&on


Rij
 qi q j
i
 j
 VElectrostatic =
4πεRij

When
other
molecules
exist
between
the
charges,
they
may
weaken
the
electrosta&c

interac&on
depending
on
the
extent
of
their
polarity.

The
more
polar
the
intervening

molecules
the
more
they
screen
the
two
charges
from
each
other.




Rij
 This
effect
is
very
important
for
water
because
water

i
 j

is
very
polar.


Charge
screening
can
be
explicitly
modeled
if
individual
waters
are
present,
or
it
can

be
approximated
implicitly
using
the
dielectric
constant
of
the
solvent.

qi q j Here
εr
is
the
rela&ve
electric
permi&vity
also
known
as
the

VElectrostatic = “dielectric
constant”.


εr Rij
For
example,
water
(very
polar,
dipole
=
1.85D)
has
a
dielectric
constant
of
80
while


n‐butanol
(less
polar,
dipole
=
1.63D)
has
a
dielectric
constant
of
18,
at
20
°C

Effect
of
Dielectric
Constant
on
Electrosta&c
Interac&on


Rij

0.000

0
 20
 40
 60
 80
 100
 120

‐0.010


‐0.020


‐0.030

Dielectric
(εr
=
80)

‐0.040

qi q j Gas
Phase

VElectrostatic = ‐0.050
 Dielectric
(εr
=
1)

εr Rij water

‐0.060


‐0.070


‐0.080


‐0.090


‐0.100


Employing
a
large
dielectric
constant
effec&vely
eliminates
electrosta&c
interac&ons


When
is
this
reasonable?
Only
when
the
charges
are
far
apart

Hydrogen
Bonding

Common
Classical
Water
Models

Hydrogen
Bonding

 Poten&al
energy
func&ons
for
atomic‐level
simula&ons

of
water
and
organic
and
biomolecular
systems

William
L.
Jorgensen
*
and
Julian
Tirado‐Rives


PNAS

May
10,
2005

vol.
102

no.
19

6665–6670


Fig.
1.
Computed
(OPLS‐AA)
and
experimental
results
for
liquid
densi&es
(Le1),
heats
of

vaporiza9on
(Middle),
and
free
energies
of
hydra9on
(Right)
at
25°C
and
1
atm.

Fig.
2.
Computed
and
experimental

results
for
the
density
(gcm3)
of

liquid
water
vs.
temperature
at

a
pressure
of
1
atm.

Example
Publica&ons:



Effects
of
water
models
on
Biomolecular
Structure


1)  Explicit
Water
Models
Affect
the
Specific
Solva7on
and
Dynamics
of

Unfolded
Pep7des
While
the
Conforma7onal
Behavior
and
Flexibility
of

Folded
Pep7des
Remain
Intact


Petra
Florov,
Petr
Sklenovsk,
Pavel
Ban,
and
Michal
Otyepka


J.
Chem.
Theory
Comput.,
2010,
6,
3569–3579



2)  On
the
role
of
water
models
in
quan7fying
the
standard
binding
free

energy
of
highly
conserved
water
molecules
in
proteins:
the
case
of

Concanavalin
A.



Elisa
Fadda
and
Robert
J.
Woods



J.
Chem.
Theory
Comput.
(2011).
In
Press.
DOI:
10.1021/ct200404z.



Summary:

Summary: