Binding of cyclic carboxylates to octa-acid deep-cavity cavitand

Gibb, Corinne L. D.; Gibb, Bruce C.

doi:10.1007/s10822-013-9690-2

Cited by 84 publications

(103 citation statements)

References 24 publications

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“…2 compared to the experimental measurements, which were not known to us prior to the submission of the predictions. [32] Trans-4-methyl-cyclohexane carboxylate (guest 7) and 4-chlorobenzoate (guest 4) are correctly predicted as the strongest and next to strongest binders in this set. The calculated binding free energies for these guests are in quantitative agreement with the experiments (for example for guest 7, −7.2 kcal/mol predicted vs. −7.6 kcal/mol experimentally).…”

Section: Results and Performancementioning

confidence: 98%

“…[32, 33] The bulk of the computational work reported here has been conducted by the students of the Statistical Thermodynamics class at the department of Chemistry at Rutgers University. The BEDAM method has been successfully applied to a variety of systems including protein-ligand binding complexes[30, 21, 34, 28] and host-guest complexes,[35] including the challenging ones presented as part of the previous SAMPL3 edition.…”

Section: Introductionmentioning

confidence: 99%

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BEDAM binding free energy predictions for the SAMPL4 octa-acid host challenge

Gallicchio

Chen

et al. 2015

J Comput Aided Mol Des

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The Binding Energy Distribution Analysis Method (BEDAM) protocol has been employed as part of the SAMPL4 blind challenge to predict the binding free energies of a set of octa-acid host-guest complexes. The resulting predictions were consistently judged as some of the most accurate predictions in this category of the SAMPL4 challenge in terms of quantitative accuracy and statistical correlation relative to the experimental values, which were not known at the time the predictions were made. The work has been conducted as part of a hands-on graduate class laboratory session. Collectively the students, aided by automated setup and analysis tools, performed the bulk of the calculations and the numerical and structural analysis. The success of the experiment confirms the reliability of the BEDAM methodology and it shows that physics-based atomistic binding free energy estimation models, when properly streamlined and automated, can be successfully employed by non-specialists.

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Section: Results and Performancementioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

BEDAM binding free energy predictions for the SAMPL4 octa-acid host challenge

Gallicchio

Chen

et al. 2015

J Comput Aided Mol Des

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“…Still, these results are somewhat affected by the use of the old experimental estimate for the Hx guest (having an error of 2.4 kJ/mol, compared to the new one). Using instead the new experimental estimate for the affinity for Hx (-23.5 kJ/mol [89]), the MAD decreases to 2.6 or 2.9 kJ/mol, whereas R 2 and 95 are not affected.…”

Section: Fep Results At the MM Levelmentioning

confidence: 99%

“…Five sets of binding affinities, calculated with different methods, were submitted to SAMPL4. Only at a later stage were the experimental affinities revealed [89]. Additional estimates, which were not submitted, will also be discussed below.…”

Section: Resultsmentioning

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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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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“…Notable new addition to a list of probable host molecules to encapsulate different gas molecules is the basket shaped octa acid (OA) synthesized by Gibb et al [1]. Many experimental and theoretical studies [2][3][4][5] have been devoted in understanding the properties of OA as well as to validate its Abstract The potential for gas storage (C 2 H 2 , C 2 H 4 , C 2 H 6 , CO 2 , CO, H 2 , N 2 , NO 2 , NO) molecules and rare gas (Rg) atoms (He n -Xe n , where n = 1, 2) within the recently synthesized octa acid (OA) moiety is assessed through density functional theory-based computations. It is shown that C 2 H 2 , C 2 H 4 , C 2 H 6 , N 2 , Kr, and Xe atoms/molecules bind with octa acid in a thermodynamically favorable way.…”

Section: Introductionmentioning

confidence: 99%