Parameterizing Small Molecules Using: The Force Field …...Mark Arcario (Tajkhorshid) with Juan...
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The Force Field Toolkit (ffTK) Christopher G. Mayne, Emad Tajkhorshid NIH Center for Macromolecular Modeling and Bioinformatics Beckman Institute for Advanced Science and Technology University of Illinois, Urbana-Champaign Parameterizing Small Molecules Using: James C. Gumbart Department of Physics Georgia Institute of Technology NIH Hands On Workshop | TCBG | April 20 th , 2017
Transcript of Parameterizing Small Molecules Using: The Force Field …...Mark Arcario (Tajkhorshid) with Juan...
2017_fftk-nih-workshop-urbana copyChristopher G. Mayne, Emad
Tajkhorshid NIH Center for Macromolecular Modeling and
Bioinformatics
Beckman Institute for Advanced Science and Technology University of Illinois, Urbana-Champaign
Parameterizing Small Molecules Using:
Georgia Institute of Technology
Σ ki (ri - r0 )2 bonds
bond Σ ( θi - θ0 )2 angles
ki angle
ki dihedral
4∈ij σij
rij 12 σij
qiqj rij
U = Ubonds Uangles Udihedrals UvdW Ucoulombic+ + + +
bonded non-bonded
Parameter set describes molecular behavior in varied chemical (connectivity) and spatial (conformation) contexts
Peptides and Proteins Nucleic Acids
repetitive backbone unit
H N N
small molecule ligands
cofactors metal centers
N
N
N
NH2
K. Vanommeslaeghe et al., J. Comput. Chem. 2010, 31, 671-690.
K. Vanommeslaeghe et al., J. Comput. Chem. 2010, 31, 671-690.
C.G. Mayne et al., J. Comput. Chem. 2013, 34, 2757-2270.
Setup & Perform Multi-dimensional Optimizations
•Auto-detect Water Interaction Sites •Auto-detect Charge Groups •Auto-detect Non-redundant Torsions •Build & Update Parameter Files •Browse Existing Parameter Sets •Write Updated Charges to PSF •Reset Opt. Input from Output
•Visualize Target Data in VMD •Create Graphic Objects in VMD •Label Atoms in VMD •Read Input Parameters from File •Read/Write Data From Opt. Logs •Export Plot Data to File •Monitor Optimization Progress
update PSF
update PAR
update PAR
Hessian Calculation (QM)
Bond & Angle Optimization
Torsion Scan (QM)
Load QM optimized geometry | Auto-detect interaction sites | Generate Gaussian Input Files | Run QM | Inspect water optimization
VMD main windowffTK GUI
Load QM optimized geometry | Auto-detect interaction sites | Generate Gaussian Input Files | Run QM | Inspect water optimization
AcceptorDonor VMD main windowffTK GUI
Generating Charge Optimization Target Data
Load QM optimized geometry | Auto-detect interaction sites | Generate Gaussian Input Files | Run QM | Inspect water optimization
Compute water position
Optimize distance & rotation
Load QM optimized geometry | Auto-detect interaction sites | Generate Gaussian Input Files | Run QM | Inspect water optimization
Visually assess QM-optimized
Optimizer: Assign Charges
Return Optimized Charges
-2
0
2
4
6
8
Assessing MM Water-Interaction Profiles
-5
-4
-3
-2
-1
0
1
2
3
4
5
6
-0.4 -0.2 0 0.2 0.4 -0.4 -0.2 0 0.2 0.4 -0.4 -0.2 0 0.2 0.4 0
500
1000
1500
2000
2500
3000
3500
4000
4500
Optimization Iteration
ffTK Enables Exciting Science
improved molecular models from low resolution x-ray data
with Mark Arcario (Tajkhorshid)
with Juan Perilla (Schulten)
mechanism of action for anti-retroviral drugs targeting the HIV capsid
with Abhi Singharoy (Schulten)
I) preparation of PSF, PDB, and initial PAR files
II) use the CGenFF Program for atom typing and “first guess” at
missing parameters
VMD Window
ffTK is available as a VMD Plugin (1.9.2 and greater) Mayne et al.; J. Comp. Chem. 2013, 34, pp. 2757-2770 (Cover Article)
Full Documentation and Screencast & Paper Tutorials http://www.ks.uiuc.edu/Research/vmd/plugins/fftk http://www.ks.uiuc.edu/Training/Tutorials/#FFTK
Volume 34 | Issues 31–32 | 2013 Included in this print edition:
Issue 31 (December 5, 2013) Issue 32 (December 15, 2013)
Research in Systems Neuroscience www.c-chem.org
COMPUTATIONAL Journal of
CHEMISTRY Organic • Inorganic • Physical Biological • Materials
Editors: Charles L. Brooks III • Masahiro Ehara • Gernot Frenking • Peter R. Schreiner
May the Force Field Be With You! http://www.ks.uiuc.edu/Highlights/?section=2013&highlight=2013-09
Beckman Institute for Advanced Science and Technology University of Illinois, Urbana-Champaign
Parameterizing Small Molecules Using:
Georgia Institute of Technology
Σ ki (ri - r0 )2 bonds
bond Σ ( θi - θ0 )2 angles
ki angle
ki dihedral
4∈ij σij
rij 12 σij
qiqj rij
U = Ubonds Uangles Udihedrals UvdW Ucoulombic+ + + +
bonded non-bonded
Parameter set describes molecular behavior in varied chemical (connectivity) and spatial (conformation) contexts
Peptides and Proteins Nucleic Acids
repetitive backbone unit
H N N
small molecule ligands
cofactors metal centers
N
N
N
NH2
K. Vanommeslaeghe et al., J. Comput. Chem. 2010, 31, 671-690.
K. Vanommeslaeghe et al., J. Comput. Chem. 2010, 31, 671-690.
C.G. Mayne et al., J. Comput. Chem. 2013, 34, 2757-2270.
Setup & Perform Multi-dimensional Optimizations
•Auto-detect Water Interaction Sites •Auto-detect Charge Groups •Auto-detect Non-redundant Torsions •Build & Update Parameter Files •Browse Existing Parameter Sets •Write Updated Charges to PSF •Reset Opt. Input from Output
•Visualize Target Data in VMD •Create Graphic Objects in VMD •Label Atoms in VMD •Read Input Parameters from File •Read/Write Data From Opt. Logs •Export Plot Data to File •Monitor Optimization Progress
update PSF
update PAR
update PAR
Hessian Calculation (QM)
Bond & Angle Optimization
Torsion Scan (QM)
Load QM optimized geometry | Auto-detect interaction sites | Generate Gaussian Input Files | Run QM | Inspect water optimization
VMD main windowffTK GUI
Load QM optimized geometry | Auto-detect interaction sites | Generate Gaussian Input Files | Run QM | Inspect water optimization
AcceptorDonor VMD main windowffTK GUI
Generating Charge Optimization Target Data
Load QM optimized geometry | Auto-detect interaction sites | Generate Gaussian Input Files | Run QM | Inspect water optimization
Compute water position
Optimize distance & rotation
Load QM optimized geometry | Auto-detect interaction sites | Generate Gaussian Input Files | Run QM | Inspect water optimization
Visually assess QM-optimized
Optimizer: Assign Charges
Return Optimized Charges
-2
0
2
4
6
8
Assessing MM Water-Interaction Profiles
-5
-4
-3
-2
-1
0
1
2
3
4
5
6
-0.4 -0.2 0 0.2 0.4 -0.4 -0.2 0 0.2 0.4 -0.4 -0.2 0 0.2 0.4 0
500
1000
1500
2000
2500
3000
3500
4000
4500
Optimization Iteration
ffTK Enables Exciting Science
improved molecular models from low resolution x-ray data
with Mark Arcario (Tajkhorshid)
with Juan Perilla (Schulten)
mechanism of action for anti-retroviral drugs targeting the HIV capsid
with Abhi Singharoy (Schulten)
I) preparation of PSF, PDB, and initial PAR files
II) use the CGenFF Program for atom typing and “first guess” at
missing parameters
VMD Window
ffTK is available as a VMD Plugin (1.9.2 and greater) Mayne et al.; J. Comp. Chem. 2013, 34, pp. 2757-2770 (Cover Article)
Full Documentation and Screencast & Paper Tutorials http://www.ks.uiuc.edu/Research/vmd/plugins/fftk http://www.ks.uiuc.edu/Training/Tutorials/#FFTK
Volume 34 | Issues 31–32 | 2013 Included in this print edition:
Issue 31 (December 5, 2013) Issue 32 (December 15, 2013)
Research in Systems Neuroscience www.c-chem.org
COMPUTATIONAL Journal of
CHEMISTRY Organic • Inorganic • Physical Biological • Materials
Editors: Charles L. Brooks III • Masahiro Ehara • Gernot Frenking • Peter R. Schreiner
May the Force Field Be With You! http://www.ks.uiuc.edu/Highlights/?section=2013&highlight=2013-09
