A hybrid quantum mechanical molecular mechanical method: Application to hydration free energy calculations

2002 ◽  
Vol 117 (6) ◽  
pp. 2762-2770 ◽  
Author(s):  
Tamer Shoeib ◽  
Giuseppe D. Ruggiero ◽  
K. W. Michael Siu ◽  
Alan C. Hopkinson ◽  
Ian H. Williams
Keyword(s):  
Free Energy ◽  
Free Energy Calculations ◽  
Quantum Mechanical ◽  
Hydration Free Energy ◽  
Mechanical Method ◽  
Energy Calculations

scholarly journals Multipole electrostatics in hydration free energy calculations

2010 ◽  
Vol 32 (5) ◽  
pp. 967-977 ◽  
Author(s):  
Yue Shi ◽  
Chuanjie Wu ◽  
Jay W. Ponder ◽  
Pengyu Ren
Keyword(s):  
Free Energy ◽  
Free Energy Calculations ◽  
Hydration Free Energy ◽  
Energy Calculations

Alchemical Hydration Free Energy Calculations Using Molecular Dynamics with Explicit Polarization and Induced Polarity Decoupling: An OTFP Approach

2019 ◽  
Author(s):  
Braden Kelly ◽  
William Smith
Keyword(s):  
Free Energy ◽  
Gas Phase ◽  
Free Energy Calculations ◽  
Partial Charge ◽  
Experimental Uncertainty ◽  
Hydration Free Energy ◽  
Energy Calculations ◽  
Lennard Jones ◽  
Partial Charges ◽  
The Cost

We present a methodology using fixed charge force–fields for alchemical solvation free energy calculations which accounts for the change in polarity that the solute experiences as it transfers from the gas-phase to the condensed phase. We update partial charges use QM/MM snapshots, decoupling the electric field appropriately when updating the partial charges. We also show how to account for the cost of self-polarization. We test our methodology on 30 molecules ranging from small polar to large drug–like molecules.We use Minimum Basis Iterative Stockholder (MBIS), Restrained Electrostatic Potential(RESP) and AM1-BCC partial charge methodologies. Using our method with MP2/cc-pVTZ and MBIS partial charges yields an AAD that is 2.98 kJ·mol−1(0.71 kcal·mol−1) lower than AM1–BCC. AM1–BCC is within experimental uncertainty on 10% of thedata compared to 40% with our method. We conjecture that results can be further improved by using Lennard–Jones and torsional parameters refitted to MBIS and RESP partial charge methods that use high levels of theory.<br>

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