Free-energy perturbation and quantum mechanical study of SAMPL4 octa-acid host-guest binding energies.
(2014) In Journal of Computer-Aided Molecular Design 28(4). p.375-400- Abstract
- We 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... (More)
- We 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 of a mismatch between the solvation energies obtained at the DFT and LCCSD(T0) levels. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4430841
- author
- Mikulskis, Paulius
LU
; Cioloboc, Daniela
; Andrejić, Milica
; Khare, Sakshi
; Brorsson, Joakim
LU
; Genheden, Samuel
LU
; Mata, Ricardo A
; Söderhjelm, Pär
LU
and Ryde, Ulf
LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Computer-Aided Molecular Design
- volume
- 28
- issue
- 4
- pages
- 375 - 400
- publisher
- Springer
- external identifiers
-
- pmid:24700414
- wos:000337043500006
- scopus:84902805310
- pmid:24700414
- ISSN
- 1573-4951
- DOI
- 10.1007/s10822-014-9739-x
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Theoretical Chemistry (S) (011001039), Department of Chemistry (011001220)
- id
- 4fa68200-2d3c-4343-b6eb-1b22501294b6 (old id 4430841)
- date added to LUP
- 2016-04-01 10:31:19
- date last changed
- 2023-01-10 00:28:30
@article{4fa68200-2d3c-4343-b6eb-1b22501294b6, abstract = {{We 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 of a mismatch between the solvation energies obtained at the DFT and LCCSD(T0) levels.}}, author = {{Mikulskis, Paulius and Cioloboc, Daniela and Andrejić, Milica and Khare, Sakshi and Brorsson, Joakim and Genheden, Samuel and Mata, Ricardo A and Söderhjelm, Pär and Ryde, Ulf}}, issn = {{1573-4951}}, language = {{eng}}, number = {{4}}, pages = {{375--400}}, publisher = {{Springer}}, series = {{Journal of Computer-Aided Molecular Design}}, title = {{Free-energy perturbation and quantum mechanical study of SAMPL4 octa-acid host-guest binding energies.}}, url = {{https://lup.lub.lu.se/search/files/1913591/5266646.pdf}}, doi = {{10.1007/s10822-014-9739-x}}, volume = {{28}}, year = {{2014}}, }