Solvation Free Energy Calculations: The Combination between the Implicitly Polarized Fixed‐charge Model and the Reference Potential Strategy

Jia, Xiangyu

doi:10.1002/jcc.26055

Cited by 7 publications

(16 citation statements)

References 65 publications

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“…This approach has also been used recently for free energy calculations by Jia and Li 35 and by Jia 35 and a modified form was used by Riquelme et al 34 Jia and Li found slightly improved results over those of the classical RESP partial charges on a small test set of molecules when using IPolQ-Mod. When correcting the endpoints using QM/MM, Jia and Li 35 and Jia 42 found the results improved and were similar to AM1-BCC. Riquelme et al's IPolQ-Mod results when using Minimal Basis Iterative Stockholder (MBIS) 49 charges rather than RESP charges achieved lackluster results in comparison with the simple and general AMBER force field (GAFF) 50 default charge method AM1-BCC, 51 and with their proposed method that used MBIS charges with post-simulation implicit polarization corrections.…”

Section: Single Simulationmentioning

confidence: 76%

“…41 The method has recently been applied to hydration free energy simulations of organic molecules and, in conjunction with the IPolQ-Mod partial charge method, yielded results similar to standard RESP and AM1-BCC free energies with GAFF on small test sets. 35,42 IPolQ is a recently developed method that calculates the electron density distribution of the solute based on measurements taken during explicit water simulation, 43 and then employs it to calculate polarized restrained electrostatic potential (RESP). 44 These charges are then averaged with charges derived for the solute in vacuum.…”

Section: Introductionmentioning

confidence: 99%

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Alchemical Hydration Free Energy Calculations Using Molecular Dynamics with Explicit Polarization and Induced Polarity Decoupling: An On-the-Fly Approach

Kelly¹,

Smith²

2020

Preprint

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<div>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 using 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 Average Absolute Deviation (AAD) of 6.3 kJ·mol−1 in comparison with the AM1-BCC result of 8.6 kJ·mol−1. AM1-BCC is within experimental uncertainty on 10% of the data compared to 30% 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.</div>

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Section: Single Simulationmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Alchemical Hydration Free Energy Calculations Using Molecular Dynamics with Explicit Polarization and Induced Polarity Decoupling: An On-the-Fly Approach

Kelly¹,

Smith²

2020

Preprint

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“…Methods to correct fixed-charge simulation free energy calculations have been under investigation for several years. [36][37][38][39][40][41] Here we compare results with one such method which also used MBIS partial charges. In the method of Riquelme et al the cost of self-polarization was calculated post-simulation and added onto the ∆G hyd calculated using standard alchemical free energy change with molecular dynamics.…”

Section: Comparison With Post-simulation Self-polarization Calculationsmentioning

confidence: 99%

“…Another approach has been to account for polarization by way of a correction to the fixed-charge FF calculation. [36][37][38][39][40][41] Whereas polarization is indirectly included in the partial charges calculated for GAFF FFs, due to its choice of ab initio theory it is not specific to any particular solvent environment. Recent work of Zhou et al 42 has shown, based on comparisons of predicted with accurate/experimental molecular dipole moments in vacuum, that HF/6-31G* exhibits inconsistencies (ranging from under-to over-polarization by as much as 35 %).…”

Section: Introductionmentioning

confidence: 99%

“…It is not possible to systematically improve the electrostatic interactions when using AM1-BCC without re-fitting the entire database of bond-charge-corrections. While AM1-BCC is the current "gold-standard" for GAFF which is used to compare alternative partial charge methods, 36,39,40 its results are in our opinion of only modest quality for solvation free energies.…”

Section: Introductionmentioning

confidence: 99%

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A Simple Method for Including Polarization Effects in Solvation Free Energy Calculations When Using Fixed-Charge Force Fields: Alchemically Polarized Charges.

Kelly

Smith²

2020

Preprint

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<div><div>The incorporation of polarizability in classical force-field molecular simulations is an ongoing area of research. We focus here on its application to hydration free energy simulations of organic molecules. In contrast to computationally complex approaches involving the development of explicitly polarizable force fields, we present herein a simple methodology for incorporating polarization into such simulations using standard fixed-charge force-fields, which we call the Alchemically Polarized Charges (APolQ) method. APolQ employs a standard classical alchemical free energy change simulation to calculate the free energy difference between a fully polarized solute particle in a condensed phase and its unpolarized state in a vacuum. One electronic structure (ES) calculation to of the electron densities is required for each state: for the former, we use a Polarizable Continuum Model (PCM), and for the latter we use vacuum-phase electronic structure calculations.</div><div><br></div><div>We applied APolQ to hydration free energy data for a test set of 45 neutral solute molecules in the FreeSolv database, and compared results obtained using three different water models (SPC/E, TIP3P, OPC3) and using MBIS and RESP partial charge methodologies. ES calculations were carried out at the MP2 level of theory and with cc-pVTZ and aug-cc-pVTZ basis sets. In comparison with AM1-BCC, we found that APolQ outperforms it for the test set. Despite our method using default GAFF parameters, the MBIS partial charges yield Absolute Average Deviations (AAD) 1.5 to 1.9 kJ·mol<sup>−1</sup> lower than AM1-BCC.</div><div><br></div><div>We conjecture that this method can be further improved by fitting the Lennard-Jones and torsional parameters to partial charges derived using MBIS or RESP methodologies. </div></div>

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Alchemical Hydration Free-Energy Calculations Using Molecular Dynamics with Explicit Polarization and Induced Polarity Decoupling: An On–the–Fly Polarization Approach

Kelly

Smith

2020

J. Chem. Theory Comput.

View full text Add to dashboard Cite

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 using 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 druglike 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 average absolute deviation (AAD) of 6.3 kJ• mol −1 in comparison with the AM1-BCC result of 8.6 kJ•mol −1 . AM1-BCC is within experimental uncertainty on 10% of the data compared to 30% 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.

show abstract

Solvation Free Energy Calculations: The Combination between the Implicitly Polarized Fixed‐charge Model and the Reference Potential Strategy

Cited by 7 publications

References 65 publications

Alchemical Hydration Free Energy Calculations Using Molecular Dynamics with Explicit Polarization and Induced Polarity Decoupling: An On-the-Fly Approach

Alchemical Hydration Free Energy Calculations Using Molecular Dynamics with Explicit Polarization and Induced Polarity Decoupling: An On-the-Fly Approach

A Simple Method for Including Polarization Effects in Solvation Free Energy Calculations When Using Fixed-Charge Force Fields: Alchemically Polarized Charges.

Alchemical Hydration Free-Energy Calculations Using Molecular Dynamics with Explicit Polarization and Induced Polarity Decoupling: An On–the–Fly Polarization Approach

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