2. modeling of small systems building the model what is the optimal conformation of a molecule? what...
Post on 19-Dec-2015
218 views
TRANSCRIPT
![Page 1: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/1.jpg)
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
![Page 2: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/2.jpg)
Modeling of small systems:building the model
database
(CSD, PDB, ICSD)
molecular editor
(Cerius, Sybyl, Molden)
neighbor
internet
set of atoms
molecule
model
connectivityhybridization
atom typescharges
atom types and chargesdepending on FF
![Page 3: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/3.jpg)
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]
![Page 4: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/4.jpg)
Modeling of small systemswhat is the optimal conformation?
E = f (ratom1, ratom2, ratom3, ratom4,……) = f (bond lengths, bond angles, torsion angles) [internal coordinates]
d1
d22
d3
t3
3
c.f. QM: Z-matrix
![Page 5: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/5.jpg)
Modeling of small systemsoptimal molecular conformation: energy minimization
energy
geometric parameter
Energy minimization may lead to…..:* the absolute E minimum* a local minimum* a saddle point; maximum* an area of almost constant energy
![Page 6: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/6.jpg)
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 theconformation of an isolated molecule look like?
![Page 7: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/7.jpg)
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.
![Page 8: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/8.jpg)
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
![Page 9: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/9.jpg)
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
![Page 10: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/10.jpg)
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
![Page 11: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/11.jpg)
Modeling of small systems Does molecule A fit into a cavity of molecule B?
ligand -- proteinadditive -- crystal surface
![Page 12: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/12.jpg)
Modeling of small systems How flexible is a molecule in solution?
Simulation of an organic salt in benzene or chloroform
![Page 13: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/13.jpg)
Molecular Dynamics (MD): from still picture to movie.
Atomic positions as a function of time, calculated by applyingNewton’s equations of motion.
r(t+ t) = r(t) + v(t+½t)tv(t+½t) = v(t-½t) + a(t)ta = F/m
Modeling of small systems Simulation of an organic salt in solution
* non-zero temperature atomic motion* system has kinetic + potential energy* equilibrium properties at T, transport properties, conformational or ‘configurational’ search
t-½t t+½tt t+t
r v r?a
v
t~1fs
![Page 14: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/14.jpg)
Modeling of small systems Simulation of an organic salt in solution
* periodic boundary conditionsto go from veeeeeeery smal dropletto ‘bulk’
* external forces/constraints: - nr. of particles - temperature - volume - pressure
NVT, NPT simulations
![Page 15: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/15.jpg)
Modeling of small systemsresults from MD
![Page 16: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/16.jpg)
Sampling methods
* Systematic: every combination of possible values of all DOF’s.* 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 sizespeed efficiency birds’ eye view
Obtaining a representative set of structures from a system withfreedom in conformation/configuration.
![Page 17: 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](https://reader036.vdocument.in/reader036/viewer/2022081515/56649d405503460f94a1a8da/html5/thumbnails/17.jpg)
Next week: Crystals!
Theorie: hoe zat dat ook al weer met die ruimtegroepen??
Experiment: wat bedoelt René de Gelder met R=6.2%?
Modeling: hoe check ik mijn model in Cerius?