using valence bond theory to model (bio)chemical...
TRANSCRIPT
September 7th 2016
1
Fernanda Duarte
Using Valence Bond Theory to Model
(Bio)Chemical Reactivity
Master Course for Theoretical Chemistry and Computational
Modelling (TCCM)
Department of Chemistry, Oxford
• Motivation & History of VB
• Basic Concepts
• ab initio VB theory
• Multiscale VB simulations
• Empirical VB theory
• Example EVB
General Outline of Lecture
3
Tutorial Q software
SN2 Reaction in Gas/Solvent Phase
PSRS
4
Tutorial Q software
Prepare
SimulateAnalyse3D Molecule (pdb)
Ffs param (lib/prm)
Solvent (opt)
Qprep
Input (.inp)
force field changes (.fep)
Topology
Qdyn
Final coord (.re)
Output MD (.log)
Energy (.en)
Trajectory (.tr)
Qfep
Free energy calc. input
Qcal
Free energy data
structure, averages,etc
5
Tutorial Q software
Prepare
3D Molecule (pdb)
Ffs param (lib/prm)
Solvent (opt)
Qprep
Topology
readlib./0-ff/qoplsaa.libreadlib./0-ff/prb.libreadlib./0-ff/cl-.libreadprm./0-ff/qoplsaa_prb_cl-.prmreadpdbprobr_cl.pdbboundarysphere1:C120#solvate1:C1201HOHmaketopprobr_cl.topwritetopprobr_cl.topwritepdbprobr_cl_start.pdbyquit
6
Tutorial Q software
[atoms]#charge1C1prc_C1-0.19842H2prc_H20.1206.........8H8prc_H80.06409H9prc_H90.064010H10prc_H100.064011Cl11prc_Cl11-0.2370[bonds]C1H2C1H3C1C4C1Cl11C4H5C4H6C4C7C7H8C7H9C7H10[impropers]
[charge_groups]C1H2H3C4H5H6Cl11C7H8H9H10
Cl
Br
Prepare
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Tutorial Q software[md]steps100000temperature300stepsize1bath_coupling100
[cut-offs]q_atom99
[files]topologyprobr_cl.toprestartrelax_002.refinalrelax_003.retrajectoryrelax_003.dcdfepprobr_cl.fep
[lambdas]1.000.00
[sequence_restraints]160.10011120.100
[distance_restraints]1110.03.53.021120.03.53.01
Simulate
Cl
Br
8
Tutorial Q software
Relaxation
9
Tutorial Q software
[FEP]states2
[atoms]#QindexPDBindex#PDBIDSTATE1TYPE11#1.C1PRB.C122#1.H2PRB.H233#1.H3PRB.H344#1.C4PRB.C455#1.H5PRB.H566#1.H6PRB.H6711#1.Br11PRB.Br11812#2.Cl1CL-.Cl1
Simulate
1
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Cl
Br
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Tutorial Q software
[change_charges]1-0.3022-0.1984#PRB.C1dq=0.103820.14410.1206#PRB.H2dq=-0.023530.14410.1206#PRB.H3dq=-0.023540.21290.2158#PRB.C4dq=0.00295-0.0082-0.0108#PRB.H5dq=-0.00266-0.0082-0.0108#PRB.H6dq=-0.00267-0.1825-1.0000#PRB.Br11dq=-0.81758-1.0000-0.2370#CL-.Cl1dq=0.7630
[soft_pairs]17#prb_C1-prb_Br1118#prc_C1-prc_Cl11
[bond_types]166.01.581.94#prb_C1-prb_Br11278.01.511.80#prc_C1-prc_Cl11
[change_bonds]11110#1.C1-1.Br11prb_C1-prb_Br11None11202#1.C1-2.Cl1Noneprc_C1-prc_Cl11
F.7 File and format descriptions F REFERENCE GUIDE
Table 13: FEP file format
[monitor groups]: Define atom groups whose non-bonded interactions are to be moni-tored (printed in the log file).1... Topology atom number of first and following atoms in group.
[monitor group pairs]: Define pairs of monitor groups whose total non-bonded interac-tions should be calculated.1 First monitor group number.2 Second monitor group number.
[bond types]: Define Q-bond types using Morse or harmonic potentials,
EMorse = De
�1� e�↵(r�r0)
�2EHarmonic =
12kb (r � r0)
2.Morse and harmonic potentials can be mixed (but each bond type is either kind). Entrieswith four values are Morse potentials and entries with three values are harmonic.
Morse potential Harmonic potential1 Q-bond type number (starting with 1).2 Morse potential dissociation energy, De
(kcal·mol�1).Harmonic force constant kb(kcal·mol�1·A�2).
3 Exponential co-e�cient ↵ in Morse poten-tial (A�2).
Equilibrium bond length r0 in har-monic potential (A).
4 Equilibrium bond length r0 in Morse po-tential (A).
[change bonds]: Assign Q-bond types. Note: shake constraints for the redefined bondsare removed. The order in which atoms are given is not important.1 Topology atom number of first atom in bond.2 Topology atom number of second atom in bond.3... Q-bond type number (referring to numbering in bond types section) or 0 to
disable bond in state 1, state 2, ...
[angle types]: Define Q-angle types.1 Q-angle type number (starting with 1).2 Harmonic force constant (kcal·mol�1·rad�2).3 Equilibrium angle (�).
[change angles]: Assign Q-angle types.1 Topology atom number of first atom in angle.2 Topology atom number of middle atom in angle.3 Topology atom number of third atom in angle.4... Q-angle type number (referring to numbering in angle types section) or 0 to
disable angle in state 1, state 2, ...
[torsion types]: Define Q-torsion types.1 Q-torsion type number (starting with 1).2 Force constant = 1
2 ·barrier height (kcal·mol�1).3 Periodicity (number of maxima per turn).4 Phase shift (�).
[change torsions]: Assign Q-torsion types. Note: The order of atoms (1, 2, 3, 4 or 4, 3,2, 1) is not important.1 Topology atom number of first atom in torsion.
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F.7 File and format descriptions F REFERENCE GUIDE
Table 13: FEP file format
[monitor groups]: Define atom groups whose non-bonded interactions are to be moni-tored (printed in the log file).1... Topology atom number of first and following atoms in group.
[monitor group pairs]: Define pairs of monitor groups whose total non-bonded interac-tions should be calculated.1 First monitor group number.2 Second monitor group number.
[bond types]: Define Q-bond types using Morse or harmonic potentials,
EMorse = De
�1� e�↵(r�r0)
�2EHarmonic =
12kb (r � r0)
2.Morse and harmonic potentials can be mixed (but each bond type is either kind). Entrieswith four values are Morse potentials and entries with three values are harmonic.
Morse potential Harmonic potential1 Q-bond type number (starting with 1).2 Morse potential dissociation energy, De
(kcal·mol�1).Harmonic force constant kb(kcal·mol�1·A�2).
3 Exponential co-e�cient ↵ in Morse poten-tial (A�2).
Equilibrium bond length r0 in har-monic potential (A).
4 Equilibrium bond length r0 in Morse po-tential (A).
[change bonds]: Assign Q-bond types. Note: shake constraints for the redefined bondsare removed. The order in which atoms are given is not important.1 Topology atom number of first atom in bond.2 Topology atom number of second atom in bond.3... Q-bond type number (referring to numbering in bond types section) or 0 to
disable bond in state 1, state 2, ...
[angle types]: Define Q-angle types.1 Q-angle type number (starting with 1).2 Harmonic force constant (kcal·mol�1·rad�2).3 Equilibrium angle (�).
[change angles]: Assign Q-angle types.1 Topology atom number of first atom in angle.2 Topology atom number of middle atom in angle.3 Topology atom number of third atom in angle.4... Q-angle type number (referring to numbering in angle types section) or 0 to
disable angle in state 1, state 2, ...
[torsion types]: Define Q-torsion types.1 Q-torsion type number (starting with 1).2 Force constant = 1
2 ·barrier height (kcal·mol�1).3 Periodicity (number of maxima per turn).4 Phase shift (�).
[change torsions]: Assign Q-torsion types. Note: The order of atoms (1, 2, 3, 4 or 4, 3,2, 1) is not important.1 Topology atom number of first atom in torsion.
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1
47
Cl
Br
11
Tutorial Q software
TS
PSRS
From G2 Method∆G‡=13.04 ; ∆G0=-5.35
12
Tutorial Q software
Analyse
Qfep
Free energy calc. input
Qcal
Free energy data
structure, averages,etc
51#numberoffiles/frames20#numberofstatesandoff-diagonals0.5961612350#kTandnumberofpointstoskip51#numberofbins10#minimumpointsforbin2.345#gasphaseshift1#numberofdiagonalelements
1276.543000#st1and2,A=Hij,mu=eta=r0=01-1#linearcomb.ofstates(E=e1-e2)
fep_000_1.000.enfep_001_0.980.en.........fep_050_0.000.enstop
V12 = Aexp{−a(r1 − r10 )2}
13
Tutorial Q software
PSRS
Bonds being Broken/Formed
14
Tutorial Q software
Bonds being Broken/Formed
Trajectory VMD
15
Tutorial Q software
Analyse
Qfep
Free energy calc. input
Qcal
Free energy data
structure, averages,etc
----------QAnalyseMapsSUMMARY---------------------Analysedwithversion:0.1.10
DIRNAMESdG#dG0RS_lTS_lPS_l1-RS_000/13.35-5.580.84000.50000.12002-TS_000/12.94-4.760.86000.50000.12003-PS_000/12.18-6.490.82000.50000.1200
Assumingnormaldistribution...
N=3MeanSt.devMediandG#12.820.5912.94dG0-5.610.87-5.58
From G2 Method
∆G‡=13.04 ; ∆G0=-5.35
16
Tutorial Q software
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Tutorial Q software
18
Tutorial Q software
19
Tutorial Q software
exp{��Gi(Xn)�} = exp{��G(�m)�}hexp{�(✏i(X
n)� "m(Xn))�}im
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Different Flavours of VB
Program Capabilities Website Comments Reference
MOLARIS-XG
EVB, FEP, AC http://laetro.usc.edu/software.html
Available for purchase from the USC
Warshel and coworkers
Q EVB, FEP, LIE http://xray.bmc.uu.se/~aqwww/q/
Free for academic use. Available upon request
Åqvist and coworkers
VM/MM VB/MMDE-VB/MM
Available upon request [email protected].
Interface program that communicates between XMVB and MOLARIS
Shurki and coworkers
MS-EVB MS-EVB In house implementation in LAMMPS MD package
Voth and coworkers
Tinker/Charmm
MS-EVB
AMBER Distributed Gaussian EVB http://ambermd.org/
AMBER license is required for GPU version
Case and coworkers