![Page 1: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/1.jpg)
Applications of SCC-DFTB method in important chemical systems
Hao HuDept. Chemistry
Duke University
![Page 2: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/2.jpg)
Outline
• Calculate relative pKa for small organic molecules
• Simulate liquid water with Divide-and-Conquer method
Accurate: bridging low-accuracy MM fields with high-level ab initio QM methods
Fast: allowing simulations of large-size molecule systems
Elstner, M. et al., Phys. Rev. B. 58:7260, 1998Frauenheim Th. et al., Phys. Stat. Sol. B 217:357, 2000
![Page 3: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/3.jpg)
pKa simulation
Acid dissociation process: BH B- + H+
Important chemical and biological significance• protein-ligand, protein-protein interactions• Protein/DNA conformational changes• Enzyme catalysis
Extensive theoretical studies based on MM force fields• Continuum solvation model• Explicit free energy simulation
Toward high-accuracy QM/MM simulations• Continuum model (Jensen group)• Explicit free energy simulation (Cui group)
![Page 4: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/4.jpg)
pKa simulation
Not such a simple problem!
Participation of water: BH + x(H2O) B- + H+(H2O)x
Unless the precise chemical composition of the hydrated proton is known, no theoretical simulation of this process is accurate.
![Page 5: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/5.jpg)
pKa simulation
Simulate relative pKa?
• Contribution of water is constant• Contribution of proton solvation is constant• Contribution of zero-point energy is constant
B1H + x(H2O) B1- + H+(H2O)x B1H B1
-G1
B2H + x(H2O) B2- + H+(H2O)x B2H B2
-
G2
G=?
![Page 6: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/6.jpg)
pKa simulation: A two-step approach
1. Dual-topology/dual-coordinate QM/MM free energy simulation with SCC-DFTB method
BH(aq) B-(aq)G4
BH(vac) B-(vac)G1
G2 G3
G4 = G3 +G1 – G2 = Gsolv +G1
Hu & Yang, J. Chem. Phys. 123:041102, 2005Similar work by Cui group
![Page 7: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/7.jpg)
pKa simulation: A two-step approach
2. Recover ab initio free energetics from SCC-DFTB simulations
BH(aq, DFT) B-(aq, DFT)G8
BH(aq,SCC-DFTB) B-(aq,SCC-DFTB)G4
G6 G7
G8 = G7 +G4 – G6
Convergence of G6 and G7 can be verified from different samples of the simulations.
6 ln exp DFT SCC DFTB SCC DFTBG kT E E
Reference potential method, Warshel group
![Page 8: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/8.jpg)
pKa simulation
Correlation between SCCDFTB and DFT energies
Methanol Methoxide
Slope=1.38 Slope=0.94
Sigma program interfaced with SCC-DFTB (2002), Gaussian03 (2005), and NWChem (2006)
![Page 9: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/9.jpg)
pKa simulation
Correlation between SCCDFTB and DFT energies
Acetic acid Acetic ion
Slope=1.08 Slope=0.95
![Page 10: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/10.jpg)
pKa simulation
Results
molecule pKaGexpr
(kcal/mol)
G4
(kcal/mol)
G8
(kcal/mol)
methanol 15.54 0.00 0.00 0.00
phenol 9.95 -7.67 -5.41 -7.22
Acetic acid 4.76 -14.79 -13.21 -16.68
![Page 11: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/11.jpg)
pKa simulation
Conclusions
1. SCC-DFTB can be applied to long time QM/MM free energy simulations to ensure the convergence of the sampling.
2. High level ab initio QM methods can be successfully applied to improve the accuracy.
3. The solute-water interaction may need further improvements: can we also simulate bulk water with SCC-DFTB method?
![Page 12: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/12.jpg)
Simulating liquid water with the Divide-and-Conquer method
![Page 13: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/13.jpg)
Water simulation
Divide-and-Conquer method: A linear-scaling approach
Each subsystem contains a central part (solid color) which is a non-overlapping portion of the whole system, plus a buffer region (light color) corresponding to other parts of the system that are within a certain distance of the central part.
Methods:Yang, W. Phys. Rev. Lett. 66:1438, 1991
Application to a protein molecule: Liu, H. et al. Proteins 44:484, 2001
![Page 14: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/14.jpg)
Water simulation
System setup
360 water molecules in a cubic box of 22.1 22.1 22.1 Å3
Temperature 298 K
Cutoff distance 8 Å
Integration step size 1 femtosecond
Constant-pressure
Some tricks
Original SCC-DFTB gives too low density
Modified gamma function gives too high density
![Page 15: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/15.jpg)
Water simulation
O-O radial distribution function (RDF) 6 60 11 exp /OOV a r a r
= 982 g/cm3 Evap = 8.3 kcal/mol
![Page 16: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/16.jpg)
Water simulation
Re-examining the water clusters
![Page 17: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/17.jpg)
Water simulation
Re-examining the water clusters
http://www-wales.ch.cam.ac.uk/~wales/CCD/anant-watcl.htmlMaheshwary, S., Patel, N., Sathyamurthy, N., Kulkarni, A. D., & Gadre, S. R., J. Phys. Chem.-A 105, 10525-10537 (2001)
![Page 18: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/18.jpg)
Water simulation
Re-examining the water clusters
![Page 19: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/19.jpg)
Water simulation
Re-examining the water clusters
![Page 20: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/20.jpg)
Water simulation
Re-examining the water clusters
6 14
HF geometry
SCC-DFTBannealing
![Page 21: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/21.jpg)
Water simulation
O-O radial distribution function (RDF)
Too many first-shell neighbors
![Page 22: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/22.jpg)
Conclusions
1. SCC-DFTB can be effectively used as a bridge between expensive, high-accuracy QM methods and low-accuracy MM force fields. SCC-DFTB can to a large extent reproduce the covalent geometries of many organic/biological molecules
2. SCC-DFTB can qualitatively describe the interactions and structure of a liquid water system. However, improvements have to be made to better model the complicated electrostatic interactions in water, including the polarization and short-range dispersion/repulsion interactions
![Page 23: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/23.jpg)
Acknowledgements
The organizers of this special symposium:
Dr. John McKelveyDr. Thomas FrauenheimDr. Marcus Elstner
Dr. Weitao Yang
Dr. Jan Hermans
Dr. Haiyan Liu
Dr. Zhenyu Lu
Mr. Ruhuai Yun
![Page 24: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/24.jpg)
If you like your graduate student,send him/her to study water;
If you hate your graduate student,send him/her to study water.
![Page 25: Applications of SCC-DFTB method in important chemical systems](https://reader036.vdocuments.us/reader036/viewer/2022062410/568159e8550346895dc73490/html5/thumbnails/25.jpg)