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Van der Spoel, DavidORCID iD iconorcid.org/0000-0002-7659-8526
Publications (10 of 112) Show all publications
Bortot, L. O., Bashardanesh, Z. & Van der Spoel, D. (2020). Making Soup: Preparing and Validating Models of the Bacterial Cytoplasm for Molecular Simulation. Journal of Chemical Information and Modeling, 60(1), 322-331
Open this publication in new window or tab >>Making Soup: Preparing and Validating Models of the Bacterial Cytoplasm for Molecular Simulation
2020 (English)In: Journal of Chemical Information and Modeling, ISSN 1549-9596, E-ISSN 1549-960X, Vol. 60, no 1, p. 322-331Article in journal (Refereed) Published
Abstract [en]

Biomolecular crowding affects the biophysical and biochemical behavior of macromolecules compared with the dilute environment in experiments on isolated proteins. Computational modeling and simulation are useful tools to study how crowding affects the structural dynamics and biological properties of macromolecules. With increases in computational power, modeling and simulation of large-scale all-atom explicit-solvent models of the prokaryote cytoplasm have now become possible. In this work, we built an atomistic model of the cytoplasm of Escherichia coli composed of 1.5 million atoms and submitted it to a total of 3 mu s of molecular dynamics simulations. The model consisted of eight different proteins representing about 50% of the cytoplasmic proteins and one type of t-RNA molecule. Properties of biomolecules under crowding conditions were compared with those from simulations of the individual compounds under dilute conditions. The simulation model was found to be consistent with experimental data about the diffusion coefficient and stability of macromolecules under crowded conditions. In order to stimulate further work, we provide a Python script and a set of files to enable other researchers to build their own E. coli cytoplasm models to address questions related to crowding.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2020
National Category
Biophysics
Identifiers
urn:nbn:se:uu:diva-406462 (URN)10.1021/acs.jcim.9b00971 (DOI)000510104100031 ()31816234 (PubMedID)
Funder
Swedish National Infrastructure for Computing (SNIC), SNIC2018-2-42
Available from: 2020-03-09 Created: 2020-03-09 Last updated: 2020-03-09Bibliographically approved
Walz, M.-M. & Van der Spoel, D. (2019). Direct Link between Structure, Dynamics, and Thermodynamics in Molten Salts. The Journal of Physical Chemistry C, 123(42), 25596-25602
Open this publication in new window or tab >>Direct Link between Structure, Dynamics, and Thermodynamics in Molten Salts
2019 (English)In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 123, no 42, p. 25596-25602Article in journal (Refereed) Published
Abstract [en]

The strongly increased use of molten salts in the energy industry necessitates knowledge of their physicochemical properties on a microscopic scale to guide the development of new technology. Here, we focus on the eutectic LiCl-KCl mixture and unravel the links between structure, dynamics, and thermodynamics and investigate both mixing and temperature effects. In the mixture, for K-Cl, an elongation of the ionic bond length is accompanied by faster ion dynamics and lower Gibbs energy of activation; the opposite is true for Li-Cl. This leads to the counter-intuitive result of retarded dynamics of the lighter ion, while the heavier ion diffusion is accelerated. In contrast, higher temperatures lead to a shortening of the cation- anion distances accompanied by faster dynamics despite an increase in the Gibbs energy of activation. Ionic bond breaking happens on the picosecond timescale and is suggested to proceed through an associative substitution mechanism because of a negative entropy of activation.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2019
National Category
Physical Chemistry
Identifiers
urn:nbn:se:uu:diva-396950 (URN)10.1021/acs.jpcc.9b07756 (DOI)000492803300008 ()
Funder
Swedish Research Council, SNIC2018-2-42eSSENCE - An eScience Collaboration
Available from: 2019-11-15 Created: 2019-11-15 Last updated: 2019-11-15Bibliographically approved
Walz, M.-M. & Van der Spoel, D. (2019). Molten alkali halides - temperature dependence of structure, dynamics and thermodynamics. Physical Chemistry, Chemical Physics - PCCP, 21(34), 18516-18524
Open this publication in new window or tab >>Molten alkali halides - temperature dependence of structure, dynamics and thermodynamics
2019 (English)In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 21, no 34, p. 18516-18524Article in journal (Refereed) Published
Abstract [en]

The renewed interest in molten salts in the energy industry fuels the need of a thorough understanding of their physicochemical properties. Alkali halide melts are perhaps the simplest ionic liquids, but they are used as electrolytes in batteries or for thermal energy storage. Although their structure is considered to be well documented and understood, a systematic evaluation of experimental structural data reveals significant discrepancies, while there is only limited experimental information on dynamic properties. Here, we investigate structure, dynamics and thermodynamic properties of pure alkali halide melts using state-of-the-art simulation models at different temperatures. The simulations provide a consistent picture of the structure of alkali halide melts with coordination numbers that lie in between experimental numbers. The simulations reveal a strengthening of the cation-anion bonds with increasing temperature that, somewhat counter-intuitively, coincides with faster dynamics in the melts. The thermodynamic analysis unveils that structure breaking proceeds on the picosecond timescale through an associative substitution mechanism as signified by a negative entropy of activation. The results on ion pair lifetimes contribute to an improved understanding of the microscopic origin of dynamical properties, such as e.g. conductivity of salt melts. The structural analysis provided here contributes to a more coherent picture of the coordination numbers in alkali halides than what is currently available from experimental data.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2019
National Category
Physical Chemistry Inorganic Chemistry
Identifiers
urn:nbn:se:uu:diva-394193 (URN)10.1039/c9cp03603b (DOI)000483701200004 ()31414083 (PubMedID)
Funder
Swedish National Infrastructure for Computing (SNIC), SNIC2017-12-41Swedish National Infrastructure for Computing (SNIC), SNIC2018-2-42eSSENCE - An eScience Collaboration
Available from: 2019-10-08 Created: 2019-10-08 Last updated: 2019-10-08Bibliographically approved
Van der Spoel, D., Manzetti, S., Haiyang, Z. & Klamt, A. (2019). Prediction of Partition Coefficients of Environmental Toxins Using Computational Chemistry Methods. ACS Omega, 4(9), 13772-13781
Open this publication in new window or tab >>Prediction of Partition Coefficients of Environmental Toxins Using Computational Chemistry Methods
2019 (English)In: ACS Omega, ISSN 2470-1343, Vol. 4, no 9, p. 13772-13781Article in journal (Refereed) Published
Abstract [en]

The partitioning of compounds between aqueous and other phases is important for predicting toxicity. Although thousands of octanol–water partition coefficients have been measured, these represent only a small fraction of the anthropogenic compounds present in the environment. The octanol phase is often taken to be a mimic of the inner parts of phospholipid membranes. However, the core of such membranes is typically more hydrophobic than octanol, and other partition coefficients with other compounds may give complementary information. Although a number of (cheap) empirical methods exist to compute octanol–water (log kOW) and hexadecane–water (log kHW) partition coefficients, it would be interesting to know whether physics-based models can predict these crucial values more accurately. Here, we have computed log kOW and log kHW for 133 compounds from seven different pollutant categories as well as a control group using the solvation model based on electronic density (SMD) protocol based on Hartree–Fock (HF) or density functional theory (DFT) and the COSMO-RS method. For comparison, XlogP3 (log kOW) values were retrieved from the PubChem database, and KowWin log kOW values were determined as well. For 24 of these compounds, log kOW was computed using potential of mean force (PMF) calculations based on classical molecular dynamics simulations. A comparison of the accuracy of the methods shows that COSMO-RS, KowWin, and XlogP3 all have a root-mean-square deviation (rmsd) from the experimental data of ≈0.4 log units, whereas the SMD protocol has an rmsd of 1.0 log units using HF and 0.9 using DFT. PMF calculations yield the poorest accuracy (rmsd = 1.1 log units). Thirty-six out of 133 calculations are for compounds without known log kOW, and for these, we provide what we consider a robust prediction, in the sense that there are few outliers, by averaging over the methods. The results supplied may be instrumental when developing new methods in computational ecotoxicity. The log kHW values are found to be strongly correlated to log kOW for most compounds.

National Category
Theoretical Chemistry
Research subject
Chemistry with Specialisation in Theoretical Chemistry
Identifiers
urn:nbn:se:uu:diva-391706 (URN)10.1021/acsomega.9b01277 (DOI)000485168200017 ()31497695 (PubMedID)
Funder
Swedish Research Council, SNIC2017-12-41
Available from: 2019-08-26 Created: 2019-08-26 Last updated: 2019-10-18Bibliographically approved
Yin, C., Cui, Z., Jiang, Y., Van der Spoel, D. & Zhang, H. (2019). Role of Host-Guest Charge Transfer in Cyclodextrin Complexation: A Computational Study. The Journal of Physical Chemistry C, 123(29), 17745-17756
Open this publication in new window or tab >>Role of Host-Guest Charge Transfer in Cyclodextrin Complexation: A Computational Study
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2019 (English)In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 123, no 29, p. 17745-17756Article in journal (Refereed) Published
Abstract [en]

Charge transfer (CT) was proposed to play a role in the cyclodextrin (CD) complexation with guest molecules. To elucidate the importance of CT interactions, here we used computational methods of quantum mechanics, docking, and molecular dynamics (MD) to investigate alpha-CD complexes with aromatic guest molecules of nitrobenzene, carboxybenzene, benzoate, 4-nitrophenol, and 4-nitrophenolate. Considering host guest CT in the docking has more of a chance to search reasonable guest orientations relative to alpha-CD matching the experiment, compared to that without CT. The CT interaction enlarges the difference in binding affinities of varied guests, as evidenced from potential of mean force (PMF) MD calculations. Energy decomposition of the total enthalpy and entropy shows the CT influence on the binding reactions in detail and indicates that there are considerable compensating effects of individual contributions from the binding partners and surrounding water. Charge transfer reduces the total dipole of alpha-CD by 9% on average and alters its dipole direction thereby affecting guest association. Gas-phase zeroth-order symmetry-adapted perturbation theory calculations show host guest CT amounts to approximately 6% of the total binding energy. The continuum solvation model based on the quantum mechanical charge density predicts binding energies comparable with the well depth of PMF profiles in explicit water. The abnormal binding strength of alpha-CD with the similar guests can be rationalized in terms of hydrogen bonding, extent of host guest CT, and dipole arrangement of guest relative to host.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2019
National Category
Physical Chemistry Theoretical Chemistry
Identifiers
urn:nbn:se:uu:diva-391363 (URN)10.1021/acs.jpcc.9b05399 (DOI)000477785000013 ()
Available from: 2019-09-24 Created: 2019-09-24 Last updated: 2019-09-24Bibliographically approved
Bashardanesh, Z., Elf, J., Zhang, H. & Van der Spoel, D. (2019). Rotational and Translational Diffusion of Proteins as a Function of Concentration. ACS OMEGA, 4(24), 20654-20664
Open this publication in new window or tab >>Rotational and Translational Diffusion of Proteins as a Function of Concentration
2019 (English)In: ACS OMEGA, E-ISSN 2470-1343, Vol. 4, no 24, p. 20654-20664Article in journal (Refereed) Published
Abstract [en]

Atomistic simulations of three different proteins at different concentrations are performed to obtain insight into protein mobility as a function of protein concentration. We report on simulations of proteins from diluted to the physiological water concentration (about 70% of the mass). First, the viscosity was computed and found to increase by a factor of 7-9 going from pure water to the highest protein concentration, in excellent agreement with in vivo nuclear magnetic resonance results. At a physiological concentration of proteins, the translational diffusion is found to be slowed down to about 30% of the in vitro values. The slow-down of diffusion found here using atomistic models is slightly more than that of a hard sphere model that neglects the electrostatic interactions. Interestingly, rotational diffusion of proteins is slowed down somewhat more (by about 80-95% compared to in vitro values) than translational diffusion, in line with experimental findings and consistent with the increased viscosity. The finding that rotation is retarded more than translation is attributed to solvent-separated clustering. No direct interactions between the proteins are found, and the clustering can likely be attributed to dispersion interactions that are stronger between proteins than between protein and water. Based on these simulations, we can also conclude that the internal dynamics of the proteins in our study are affected only marginally under crowding conditions, and the proteins become somewhat more stable at higher concentrations. Simulations were performed using a force field that was tuned for dealing with crowding conditions by strengthening the protein-water interactions. This force field seems to lead to a reproducible partial unfolding of an alpha-helix in one of the proteins, an effect that was not observed in the unmodified force field.

National Category
Biophysics
Identifiers
urn:nbn:se:uu:diva-395115 (URN)10.1021/acsomega.9b02835 (DOI)000502130800028 ()31858051 (PubMedID)
Funder
Swedish Research Council, 2013-5947Swedish National Infrastructure for Computing (SNIC), SNIC2017-12-41
Available from: 2019-10-12 Created: 2019-10-12 Last updated: 2020-01-23Bibliographically approved
Walz, M.-M. & Van der Spoel, D. (2019). Systematically improved melting point prediction: a detailed physical simulation model is required. Chemical Communications, 55(80), 12044-12047
Open this publication in new window or tab >>Systematically improved melting point prediction: a detailed physical simulation model is required
2019 (English)In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 55, no 80, p. 12044-12047Article in journal (Refereed) Published
Abstract [en]

Accurate prediction of fundamental properties such as melting points using direct physical simulation is challenging. Here, we investigate the melting point (T-m) of alkali halides that are often considered to be the simplest category of salts. Popular force fields that have been examined for this task leave considerable room for improvement. Recently we introduced a new force field for alkali halides (WBK) as part of the Alexandria project, featuring explicit polarisation and distributed charges. This new force field significantly improves the prediction of a large set of physicochemical properties and in this contribution we show that the same is valid for the prediction of T-m. For reference, we calculated T-m using a non-polarisable force field by Joung and Cheatham (JC), and compare our results to existing literature data on the widely used Tosi-Fumi (TF) parameters. In contrast to the predictions of the WBK model, the JC force field consistently overestimates the experimental T-m, while the accuracy of the TF model strongly depends on the investigated salt. Our results show that the inclusion of more realistic physics into a force field opens up the possibility to accurately describe many physicochemical properties over a large range of temperatures, even including phase transitions.

National Category
Theoretical Chemistry
Identifiers
urn:nbn:se:uu:diva-397939 (URN)10.1039/c9cc06177k (DOI)000496529500011 ()31532407 (PubMedID)
Funder
Swedish Research Council, SNIC2017-12-41Swedish Research Council, SNIC2018-2-42
Available from: 2020-01-02 Created: 2020-01-02 Last updated: 2020-01-02Bibliographically approved
Elofsson, A., Hess, B., Lindahl, E., Onufriev, A., Van der Spoel, D. & Wallqvist, A. (2019). Ten simple rules on how to create open access and reproducible molecular simulations of biological systems. PloS Computational Biology, 15(1), Article ID e1006649.
Open this publication in new window or tab >>Ten simple rules on how to create open access and reproducible molecular simulations of biological systems
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2019 (English)In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 15, no 1, article id e1006649Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2019
National Category
Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:uu:diva-377803 (URN)10.1371/journal.pcbi.1006649 (DOI)000457372500019 ()30653494 (PubMedID)
Available from: 2019-02-27 Created: 2019-02-27 Last updated: 2019-02-27Bibliographically approved
Zhang, H., Yin, C., Jiang, Y. & van der Spoel, D. (2018). Force Field Benchmark of Amino Acids: I. Hydration and Diffusion in Different Water Models. Journal of Chemical Information and Modeling, 58(5), 1037-1052
Open this publication in new window or tab >>Force Field Benchmark of Amino Acids: I. Hydration and Diffusion in Different Water Models
2018 (English)In: Journal of Chemical Information and Modeling, ISSN 1549-9596, E-ISSN 1549-960X, Vol. 58, no 5, p. 1037-1052Article in journal (Refereed) Published
Abstract [en]

Thermodynamic and kinetic properties are of critical importance for the applicability of computational models to biomolecules such as proteins. Here we present an extensive evaluation of the Amber ff99SB-ILDN force field for modeling of hydration and diffusion of amino acids with three-site (SPC, SPC/E, SPC/E-b , and TIP3P), four-site (TIP4P, TIP4P-Ew, and TIP4P/2005), and five-site (TIPSP and TIP5P-Ew) water models. Hydration free energies (HFEs) of neutral amino acid side chain analogues have little dependence on the water model, with a root-mean-square error (RMSE) of similar to 1 kcal/mol from experimental observations. On the basis of the number of interacting sites in the water model, HFEs of charged side chains can be putatively classified into three groups, of which the group of three-site models lies between those of four- and five-site water models; for each group, the water model dependence is greatly eliminated when the solvent Galvani potential is considered. Some discrepancies in the location of the first hydration peak (R-RDF) in the ion-water radial distribution function between experimental and calculated observations were detected, such as a systematic underestimation of the acetate (Asp side chain) ion. The RMSE of calculated diffusion coefficients of amino acids from experiment increases linearly with the increasing diffusion coefficients of the solvent water models at infinite dilution. TIP3P has the fastest diffusivity, in line with literature findings, while the "FB" and "OPC" water model families as well as TIP4P/2005 perform well, within a relative error of 5%, and TIP4P/2005 yields the most accurate estimate for the water diffusion coefficient. All of the tested water models overestimate amino acid diffusion coefficients by approximately 40% (TIP4P/2005) to 200% (TIP3P). Scaling of protein-water interactions with TIP4P/2005 in the Amber ff99SBws and ff03ws force fields leads to more negative HFEs but has little influence on the diffusion of amino acids. The most recent FF/water combinations of ff14SB/OPC3, ffl5ipq/SPC/E-b, and fb15/TIP3P-FB do not show obvious improvements in accuracy for the tested quantities. These findings here establish a benchmark that may aid in the development and improvement of classical force fields to accurately model protein dynamics and thermodynamics.

National Category
Physical Chemistry
Identifiers
urn:nbn:se:uu:diva-357575 (URN)10.1021/acs.jcim.8b00026 (DOI)000433634900013 ()29648448 (PubMedID)
Funder
Swedish Research Council, 2013-5947
Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-08-17Bibliographically approved
Bashardanesh, Z. & van der Spoel, D. (2018). Impact of Dispersion Coefficient on Simulations of Proteins and Organic Liquids. Journal of Physical Chemistry B, 122(33), 8018-8027
Open this publication in new window or tab >>Impact of Dispersion Coefficient on Simulations of Proteins and Organic Liquids
2018 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 122, no 33, p. 8018-8027Article in journal (Refereed) Published
Abstract [en]

In the context of studies of proteins under crowding conditions, it was found that there is a tendency of simulated proteins to coagulate in a seemingly unphysical manner. This points to an imbalance in the protein-protein or protein-water interactions. One way to resolve this is to strengthen the protein-water Lennard-Jones interactions. However, it has also been suggested that dispersion interactions may have been systematically overestimated in force fields due to parameterization with a short cutoff. Here, we test this proposition by performing simulations of liquids and of proteins in solution with systematically reduced C-6 (dispersion constant in a 12-6 Lennard-Jones potential) and evaluate the properties. We find that simulations of liquids with either a dispersion correction or explicit long-range Lennard-Jones interactions need little or no correction to the dispersion constant to reproduce the experimental density. For simulations of proteins, a significant reduction in the dispersion constant is needed to reduce the coagulation, however. Because the protein- and liquid force fields share atom types, at least to some extent, another solution for the coagulation problem may be needed, either through including explicit polarization or through strengthening protein-water interactions.

National Category
Physical Chemistry Biophysics
Identifiers
urn:nbn:se:uu:diva-364048 (URN)10.1021/acs.jpcb.8b05770 (DOI)000442959900008 ()30084244 (PubMedID)
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2019-10-14Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-7659-8526

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