PREDICCIÓN DE ESTRUCTURAS DE CRISTALES CON MOLÉCULAS PREDICCIÓN DE ESTRUCTURAS DE CRISTALES CON MOLÉCULAS FLEXIBES EN SU CELDAFLEXIBES EN SU CELDA
V. Bazterra, M. B. Ferraro,
J. C. Facelli
Departamento de Física
Facultad de Ciencias Exactas y Naturales
Universidad de Buenos Aires
2007
Crystal engeneering
Pharmaceutical design
Polymorphism Application in materials.
AIM OF THE APPLICATIONAIM OF THE APPLICATION
Why GENETIC ALGORITHMS?
Useful to model atomic and molecular clusters.
Difficult crystal prediction from first principles.
Polymorphic forms in organic crystals
MGAC Crystal Structure Prediction CapabilitiesMGAC Crystal Structure Prediction CapabilitiesVictor E. Bazterra, Matthew Thorley, Marta B. Ferraro, Victor E. Bazterra, Matthew Thorley, Marta B. Ferraro,
and Julio C. Facelliand Julio C. FacelliJ. Chem. Theory Comput. J. Chem. Theory Comput. 2007, 2007, 3, 3, 201-209201-209
Search for crystal structures within Search for crystal structures within any symmetry groupany symmetry group and with an and with an arbitrary number of moleculesarbitrary number of molecules and molecular types per asymmetric and molecular types per asymmetric unit.unit.
Search structures using either the Search structures using either the rigid or flexiblerigid or flexible molecule models. molecule models.
Automatically Automatically generate the molecule’s generate the molecule’s force fieldforce field using existing force using existing force field libraries.field libraries.
Increase the sampling power and the complexity of molecules amenable Increase the sampling power and the complexity of molecules amenable
to CSP studies using the to CSP studies using the parallel and distributedparallel and distributed computing computing capabilities of the system.capabilities of the system.
Automatically compare, sort and archiveAutomatically compare, sort and archive the most relevant structures the most relevant structures in a user database.in a user database.
GENETIC CODING
Molecular center of mass {R1, R2,…Rn}
Its orientations {1 , 2 ,… \n }
Relevant dihedral angles {1 , 2 , …..n }
Space group and lattice parameters {a,b,c,,,}
(Rigid bodies)
SEMI-RIGID APPROXIMATIONSEMI-RIGID APPROXIMATION
DATA
-Crystallographic group
-Number of molecules in the cell
PARAMETERS
-Lattice angles, , ,
-Lattice axis a, b, c
APTITUDE FUNCTION-AMBER FORCE FIELD -CHARMm FORCE FIELD
in CHARMM code
MOLECULES:-center of mass positions-relative orientations
SEMIRIGID APPROXIMATIONSEMIRIGID APPROXIMATION
Rigid bodies with flexible chains
Parameters to be optimized
-crystallographic cell axes and angles.
-positions of the center of masss of each molecule.
-Euler angles respect to the unit cell.
-Ndihe molecular angles.
K=6+Z(6+Ndihed.)
Benzene
-51-50-49-48-47-46-45-44-43-42-41-40
1 4 7
10
13
16
19
22
25
28
31
Generations
En
erg
y[k
J/m
ol]
Average EnergyMaximum EnergyMinimum Energy
Benzene
010203040
50607080
-50 -49 -48 -47 -46
Energy [kJ/mol]
Nu
m. i
nd
ivid
ual
s
Evolution of the population energy
Hystogram of the evolution
Population analysisPopulation analysis
Local optimization using CHARMM 6, 7 with the GAFF 14 parameters. Local optimization using CHARMM 6, 7 with the GAFF 14 parameters. cutoff of 14 Å, and the electrostatic interactions were calculated using cutoff of 14 Å, and the electrostatic interactions were calculated using the Ewald technique. the Ewald technique.
Atomic charges, , using the restrained electrostatic potential approach Atomic charges, , using the restrained electrostatic potential approach implemented on the RESP program. Gaussian03 32 package at HF/6-implemented on the RESP program. Gaussian03 32 package at HF/6-31G* level.31G* level.
Restricted searches using 30 individuals in the population for up to 130 Restricted searches using 30 individuals in the population for up to 130 generations, for the 14 most common symmetry groups for organic generations, for the 14 most common symmetry groups for organic molecules, P1, P-1, P21, C2, Pc, Cc, P21/c, C2/c, P212121, Pca21, Pna21, molecules, P1, P-1, P21, C2, Pc, Cc, P21/c, C2/c, P212121, Pca21, Pna21, Pbcn, Pbca and Pnma. Pbcn, Pbca and Pnma.
For each molecule we performed between 150 and 200 runs leading to at For each molecule we performed between 150 and 200 runs leading to at least 100 complete runs with 130 generations. least 100 complete runs with 130 generations.
From these short lists we manually detected clearly unphysical From these short lists we manually detected clearly unphysical structures and duplicated ones that were not eliminated in the previous structures and duplicated ones that were not eliminated in the previous step that were identified by comparison of their XRPD spectra step that were identified by comparison of their XRPD spectra
CSP2007 MethodologyCSP2007 Methodology
Molecule XIIMolecule XII
EXP.EXP.Acry02 (Pbca)Acry02 (Pbca)
PredictedPredictedCrystal_051_050 (Pbca)Crystal_051_050 (Pbca)
aa 6.764 (6.764 (6.9706.970)) 6.7646.764
bb 9.866 (9.866 (9.7529.752)) 9.8669.866
cc 9.536 (9.536 (9.5149.514)) 9.5369.536
9090 9090
9090 9090
9090 9090
RMS (RMS (Å)Å) 0.2458170.245817
ENERGY (kJ/mol)ENERGY (kJ/mol) -22.402-22.402 -22.402-22.402
Molecule XIVMolecule XIVExp.Exp.
Alphyph Alphyph (P21/c)(P21/c)
Predic.Predic.Crystal_06_006 Crystal_06_006
(P21, P21/c)(P21, P21/c)
aa 14.042 14.042 ((13.06013.060))
14.882, 14.046 14.882, 14.046
bb 9.613 9.613 (9.738(9.738))
9.612, 9.6129.612, 9.612
cc 8.264 8.264 ( ( 9.3359.335))
9.551, 8.2639.551, 8.263
9090 90, 9090, 90
100.9 100.9 ((105.8105.8))
1156.942, 100.9456.942, 100.94
9090 90, 9090, 90
RMS (RMS (Å)Å) 0.8301750.830175
ENERGY ENERGY (kJ/mol)(kJ/mol)
- 19.660 - 19.660 -19.675-19.675
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Test predictions of benchmark crystalsTest predictions of benchmark crystals
Prediction of experimental dataPrediction of experimental data
Incorporation of additional Incorporation of additional pseudopotentialspseudopotentials
Cosmetics and website.Cosmetics and website.