Free energies of solvation with quantum mechanical interaction energies from classical mechanical simulations

Wood, Robert H.; Yezdimer, Eric M.; Sakane, Shinichi; Barriocanal, José A.; Doren, Douglas J.

doi:10.1063/1.478009

Cited by 79 publications

(85 citation statements)

References 28 publications

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“…7), which would give a QTCP-like approach. Similar corrections have been used in similar contexts before [68][69][70][71][72][73][74]. Unfortunately, such an approach becomes unstable if the differences between the MM and QM potentials are too large, leading to corrections that depend only in a few of the DFT calculations [90].…”

Section: Fep Results At the Dft-d3 Levelmentioning

confidence: 99%

“…We use two types of approaches to get around this problem and still retain the rigorousness. The first type is an endpoint approach, previously applied in reference-potential methods such as QM/FEP, QTCP (QM/MM thermodynamic cycle perturbation), and paradynamics [68,69,70,71,72,73,74]. Here, a thermodynamic cycle is used to obtain…”

Section: Dft-d Fep Calculationsmentioning

confidence: 99%

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Free-energy perturbation and quantum mechanical study of SAMPL4 octa-acid host–guest binding energies

Mikulskis

Cioloboc

Andrejić

et al. 2014

J Comput Aided Mol Des

220

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Free-energy perturbation and quantum mechanical study of SAMPL4 octa-acid hostguest binding energies. Link to publication Citation for published version (APA): Mikulskis, P., Cioloboc, D., Andrejić, M., Khare, S., Brorsson, J., Genheden, S., ... Ryde, U. (2014). Free-energy perturbation and quantum mechanical study of SAMPL4 octa-acid host-guest binding energies. Journal of Computer-Aided Molecular Design, 28(4), 375-400. DOI: 10.1007/s10822-014-9739-x General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal AbstractWe have estimated free energies for the binding of nine cyclic carboxylate guest molecules to the octa-acid host in the SAMPL4 blind-test challenge with four different approaches. First, we used standard free-energy perturbation calculations of relative binding affinities, performed at the molecular-mechanics (MM) level with TIP3P waters, the GAFF force field, and two different sets of charges for the host and the guest, obtained either with the restrained electrostatic potential or AM1-BCC methods. Both charge sets give good and nearly identical results, with a mean absolute deviation (MAD) of 4 kJ/mol and a correlation coefficient (R 2 ) of 0.8 compared to experimental results. Second, we tried to improve these predictions with 28 800 density-functional theory (DFT) calculations for selected snapshots and the non-Boltzmann Bennett acceptance-ratio method, but this led to much worse results, probably because of a too large difference between the MM and DFT potential-energy functions. Third, we tried to calculate absolute affinities using minimised DFT structures. This gave intermediate-quality results with MADs of 5-9 kJ/mol and R 2 = 0.6-0.8, depending on how the structures were obtained. Finally, we tried to improve these results using local coupled-cluster calculations with single and double excitations, and non-iterative perturbative treatment of triple excitations (LCCSD(T0)), employing the polarisable multipole interactions with supermolecular pairs approach. Unfortunately, this only degraded the predictions, probably because a mismatch between the solvation energies obtained at the DFT and LCCSD(T0) levels.Key Words: binding affinities, host-guest, free-energies perturbation, density-functional calculations, CCSD(T), polarisable multipole interactions. 2 IntroductionOne of the largest challenges of computational chemistry is to predict the binding affinity of a small ligand to a larger receptor molecule, e.g. a drug candidate to its receptor prot...

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Section: Fep Results At the Dft-d3 Levelmentioning

confidence: 99%

Section: Dft-d Fep Calculationsmentioning

confidence: 99%

Free-energy perturbation and quantum mechanical study of SAMPL4 octa-acid host–guest binding energies

Mikulskis

Cioloboc

Andrejić

et al. 2014

J Comput Aided Mol Des

220

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“…The accuracy of these calculations depends sensitively on the classical model potential used, however. In the same spirit as Doren, Wood, and coworkers, 11,12,13,14 we are interested in incorporating quantum mechanical calculations in the study of the thermodynamics of ions in water and near proteins. The basic idea in Refs.…”

Section: Introductionmentioning

confidence: 99%

“…The basic idea in Refs. 11,12,13,14 is to perform classical simulations, obtain the free energy from those classical simulations, and then use the classical configurations coupled with statistical mechanical perturbation theory to correct those free energies towards the quantum result. This method is less expensive than a direct ab initio molecular dynamics (AIMD) quantum simulation 15,16,17,18 since it uses a classical simulation to generate configurations for thermal averages.…”

Section: Introductionmentioning

confidence: 99%

Polarization and charge transfer in the hydration of chloride ions

Zhao

Rogers

Beck

2010

The Journal of Chemical Physics

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A theoretical study of the structural and electronic properties of the chloride ion and water molecules in the first hydration shell is presented. The calculations are performed on an ensemble of configurations obtained from molecular dynamics simulations of a single chloride ion in bulk water. The simulations utilize the polarizable AMOEBA force field for trajectory generation, and MP2-level calculations are performed to examine the electronic structure properties of the ions and surrounding waters in the external field of more distant waters. The ChelpG method is employed to explore the effective charges and dipoles on the chloride ions and first-shell waters. The Quantum Theory of Atoms in Molecules (QTAIM) is further utilized to examine charge transfer from the anion to surrounding water molecules. The clusters extracted from the AMOEBA simulations exhibit high probabilities of anisotropic solvation for chloride ions in bulk water. From the QTAIM analysis, 0.2 elementary charges are transferred from the ion to the first-shell water molecules. The default AMOEBA model overestimates the average dipole moment magnitude of the ion compared with the estimated quantum mechanical value. The average magnitude of the dipole moment of the water molecules in the first shell treated at the MP2 level, with the more distant waters handled with an AMOEBA effective charge model, is 2.67 D. This value is close to the AMOEBA result for first-shell waters (2.72 D) and is slightly reduced from the bulk AMOEBA value (2.78 D). The magnitude of the dipole moment of the water molecules in the first solvation shell is most strongly affected by the local water-water interactions and hydrogen bonds with the second solvation shell, rather than by interactions with the ion.

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“…26,56 In the study of Liu et al, the energies of 57 trimers randomly selected from liquid state simulations plus some selected for a specific geometry were compared using electronic structure methods ͑Hartree-Fock with 6-31G** basis sets and local Mo "ller-Plesset second-order perturbation theory͒ and the fluctuating data TIP4P-FQ potential. 21 For the strength of the three-body interactions, which are up to 1 kcal/mol or 10% of the trimer binding energy, the FQ model agrees as well with the electronic structure methods.…”

Section: Introductionmentioning

confidence: 99%

Simulations of ice and liquid water over a range of temperatures using the fluctuating charge model

Rick

2001

The Journal of Chemical Physics

178

159

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Simulations of ice and liquid water over a range of temperatures using the fluctuating charge model The temperature dependence of the thermodynamic and dynamical properties of liquid water using the polarizable fluctuating charge ͑FQ͒ model is presented. The properties of ice Ih, both for a perfect lattice with no thermal disorder and at a temperature of 273 K, are also presented. In contrast to nonpolarizable models, the FQ model has a density maximum of water near 277 K. For ice, the model has a dipole moment of the perfect lattice of 3.05 Debye, in good agreement with a recent induction model calculation. The simulations at 273 K and the correct density find that thermal motion decreases the average dipole moment to 2.96 D. The liquid state dipole moment is less than the ice value and decreases with temperature.

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Free energies of solvation with quantum mechanical interaction energies from classical mechanical simulations

Cited by 79 publications

References 28 publications

Free-energy perturbation and quantum mechanical study of SAMPL4 octa-acid host–guest binding energies

Free-energy perturbation and quantum mechanical study of SAMPL4 octa-acid host–guest binding energies

Polarization and charge transfer in the hydration of chloride ions

Simulations of ice and liquid water over a range of temperatures using the fluctuating charge model

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