2. Modeling of small systems

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2. Modeling of small systems
Building the model What is the optimal
conformation of a molecule? What is the relative
energy of a given conformation? What does the
charge distribution look like? Does a molecule
form dimers? Does molecule A fit into a cavity
of molecule B? How flexible is a molecule in
solution? Sampling methods
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Modeling of small systemsbuilding the model
database (CSD, PDB, ICSD)
molecular editor (Cerius, Sybyl, Molden)
neighbor internet
set of atoms
connectivity hybridization
molecule
atom types charges
atom types and charges depending on FF
model
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Modeling of small systemswhat is the optimal
conformation?
optimal conformation average geometry at room
temperature optimal conformation structure with
the lowest MM energy optimizing a structure ?
minimizing the MM energy
E f (geometry) f (ratom1, ratom2, ratom3,
ratom4,) atomic
coordinates f (bond lengths, bond angles,
torsion angles) internal coordinates
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Modeling of small systemswhat is the optimal
conformation?
E f (ratom1, ratom2, ratom3, ratom4,) f
(bond lengths, bond angles, torsion angles)
internal coordinates
?3
d3
t3
d2
?2
d1
c.f. QM Z-matrix
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Modeling of small systemsoptimal molecular
conformation energy minimization
energy
Energy minimization may lead to.. the
absolute E minimum a local minimum a saddle
point maximum an area of almost constant
energy
geometric parameter
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Modeling of small systemsoptimal molecular
conformation energy minimization
Common applications Cleaning up structures
from the CSD ( remove errors in e.g. H
positions) Identifying packing effects what
does the conformation of an isolated molecule
look like?
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Modeling of small systems What is the relative
energy of a given conformation?
?
calculate E(?)
Calculate E, while setting ? to 0, 15, 30, 45,
... bumping atoms will cause unrealistic, high
energy barriers. ? relax (optimize) rest of
structure, given ? . How likely is each
conformation. How easily can they interconvert.
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Modeling of small systems conformational energy
with/without solvent
E(?). in water? in vacuum? in benzene?
?
No solvent included in simulation
intra-molecular H bonds emphasized molecule
tends to contract
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Modeling of small systems What does the charge
distribution look like?
how polar is the molecule? how large is the
dipole moment? which interactions can be
anticipated?
example alizarine/NaCl
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Modeling of small systems Does a molecule form
dimers?
does a molecule dock well onto itself?
geometric fitting / steric hindrance close
contacts. favorable electrostatics H-bonds?
energy minimization in vacuo
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Modeling of small systems Does molecule A fit
into a cavity of molecule B?
ligand -- protein additive -- crystal surface
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Modeling of small systems How flexible is a
molecule in solution?Simulation of an organic
salt in benzene or chloroform
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Modeling of small systems Simulation of an
organic salt in solution
Molecular Dynamics (MD) from still picture to
movie. Atomic positions as a function of time,
calculated by applying Newtons equations of
motion. r(t ?t) r(t) v(t½?t)?t v(t½?t)
v(t-½?t) a(t)?t a F/m
a
r
v
r?
v
t?t
t½?t
t
t-½?t
?t1fs
non-zero temperature ? atomic motion system
has kinetic potential energy equilibrium
properties at T, transport properties,
conformational or configurational search
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Modeling of small systems Simulation of an
organic salt in solution
periodic boundary conditions to go from
veeeeeeery smal droplet to bulk external
forces/constraints - nr. of particles -
temperature - volume - pressure NVT, NPT
simulations
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Modeling of small systemsresults from MD
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Sampling methods
Obtaining a representative set of structures from
a system with freedom in conformation/configuratio
n.
Systematic every combination of possible
values of all DOFs. Random a random subset of
the above. MD frames taken every n ps from
an MD run. MC frames taken from an MC
run. Properties/features simplicity completeness
grid size speed efficiency birds eye view
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Next week Crystals!
Theorie hoe zat dat ook al weer met die
ruimtegroepen?? Experiment wat bedoelt René de
Gelder met R6.2? Modeling hoe check ik mijn
model in Cerius?