| 1. |
- Nicholls, Ian A., et al.
(författare)
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Rational design of biomimetic molecularly imprinted materials : theoretical and computational strategies for guiding nanoscale structured polymer development
- 2011
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 400:6, s. 1771-1786
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Forskningsöversikt (refereegranskat)abstract
- In principle, molecularly imprinted polymer science and technology provides a means for ready access to nano-structured polymeric materials of predetermined selectivity. The versatility of the technique has brought it to the attention of many working with the development of nanomaterials with biological or biomimetic properties for use as therapeutics or in medical devices. Nonetheless, the further evolution of the field necessitates the development of robust predictive tools capable of handling the complexity of molecular imprinting systems. The rapid growth in computer power and software over the past decade has opened new possibilities for simulating aspects of the complex molecular imprinting process. We present here a survey of the current status of the use of in silico-based approaches to aspects of molecular imprinting. Finally, we highlight areas where ongoing and future efforts should yield information critical to our understanding of the underlying mechanisms sufficient to permit the rational design of molecularly imprinted polymers.
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| 2. |
- Wiklander, Jesper G., 1974-, et al.
(författare)
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Towards a synthetic avidin mimic
- 2011
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 400:5, s. 1397-1404
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Tidskriftsartikel (refereegranskat)abstract
- A series of streptavidin-mimicking molecularly imprinted polymers has been developed and evaluated for their biotin binding characteristics. A combination of molecular dynamics and NMR spectroscopy was used to examine potential polymer systems, in particular with the functional monomers methacrylic acid and 2-acrylamidopyridine. The synthesis of copolymers of ethylene dimethacrylate and one or both of these functional monomers was performed. A combination of radioligand binding studies and surface area analyses demonstrated the presence of selectivity in polymers prepared using methacrylic acid as the functional monomer. This was predicted by the molecular dynamics studies showing the power of this methodology as a prognostic tool for predicting the behavior of molecularly imprinted polymers.
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| 3. |
- Ahlstrand, Emma, et al.
(författare)
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Computer simulations of alkali-acetate solutions : Accuracy of the forcefields in difference concentrations
- 2017
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Ingår i: Journal of Chemical Physics. - : American Institute of Physics (AIP). - 0021-9606 .- 1089-7690. ; 147, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- When proteins are solvated in electrolyte solutions that contain alkali ions, the ions interact mostlywith carboxylates on the protein surface. Correctly accounting for alkali-carboxylate interactionsis thus important for realistic simulations of proteins. Acetates are the simplest carboxylates thatare amphipathic, and experimental data for alkali acetate solutions are available and can be comparedwith observables obtained from simulations. We carried out molecular dynamics simulations of alkali acetate solutions using polarizable and non-polarizable forcefields and examined the ionacetateinteractions. In particular, activity coefficients and association constants were studied in a range of concentrations (0.03, 0.1, and 1M). In addition, quantum-mechanics (QM) based energy decomposition analysis was performed in order to estimate the contribution of polarization, electrostatics, dispersion, and QM (non-classical) effects on the cation-acetate and cation-water interactions. Simulations of Li-acetate solutions in general overestimated the binding of Li+ and acetates. In lower concentrations, the activity coefficients of alkali-acetate solutions were too high, which is suggested to be due to the simulation protocol and not the forcefields. Energy decomposition analysis suggested that improvement of the forcefield parameters to enable accurate simulations of Li-acetate solution scan be achieved but may require the use of a polarizable forcefield. Importantly, simulations with some ion parameters could not reproduce the correct ion-oxygen distances, which calls for caution in thechoice of ion parameters when protein simulations are performed in electrolyte solutions.
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| 4. |
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| 5. |
- Becconi, Olga, et al.
(författare)
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Protein-ion Interactions : Simulations of Bovine Serum Albumin in Physiological Solutions of NaCl, KCl and LiCl
- 2017
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Ingår i: Israel Journal of Chemistry. - : Wiley-Blackwell. - 0021-2148. ; 57:5, s. 403-412
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Tidskriftsartikel (refereegranskat)abstract
- Specific interactions that depend on the nature of electrolytes are observed when proteins and other molecules are studied by potentiometric, spectroscopic and theoretical methods at high salt concentrations. More recently, it became clear that such interactions may also be observed in solutions that can be described by the Debye-Hückel theory, i.e., at physiological (0.1 mol dm−3) and lower concentrations. We carried out molecular dynamics simulations of bovine serum albumin in physiological solutions at T=300 and 350 K. Analysis of the simulations revealed some differences between LiCl solutions and those of NaCl and KCl. The binding of Li+ ions to the protein was associated with a negative free energy of interaction whereas much fewer Na+ and K+ ions were associated with the protein surface. Interestingly, unlike other proteins BSA does not show a preference to Na+ over K+. Quantum chemical calculations identified a significant contribution from polarisation to the hydration of Li+ and (to a lesser degree) Na+, which may indicate that polarisable force-fields will provide more accurate results for such systems.
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| 6. |
- Friedman, Ran, et al.
(författare)
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Discovery of plasmepsin inhibitors by fragment-based docking and consensus scoring
- 2009
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Ingår i: ChemMedChem. - : Wiley. - 1860-7179 .- 1860-7187. ; 4:8, s. 1317-1326
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Tidskriftsartikel (refereegranskat)abstract
- Plasmepsins (PMs) are essential proteases of the plasmodia parasites and are therefore promising targets for developing drugs against malaria. We have discovered six inhibitors of PM II by high-throughput fragment-based docking of a diversity set of ∼40 000 molecules, and consensus scoring with force field energy functions. Using the common scaffold of the three most active inhibitors (IC50=2–5 μM), another seven inhibitors were identified by substructure search. Furthermore, these 13 inhibitors belong to at least three different classes of compounds. The in silico approach was very effective since a total of 13 active compounds were discovered by testing only 59 molecules in an enzymatic assay. This hit rate is about one to two orders of magnitude higher than those reported for medium- and high-throughput screening techniques in vitro. Interestingly, one of the inhibitors identified by docking was halofantrine, an antimalarial drug of unknown mechanism. Explicit water molecular dynamics simulations were used to discriminate between two putative binding modes of halofantrine in PM II.
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| 7. |
- Friedman, Ran
(författare)
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Ions and the protein surface revisited : extensive molecular dynamics simulations and analysis of protein structures in alkali-chloride solutions
- 2011
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 115, s. 9213-9223
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Tidskriftsartikel (refereegranskat)abstract
- Proteins interact with ions in various ways. The surface of proteins has an innate capability to bind ions, and it is also influenced by the screening of the electrostatic potential owing to the presence of salts in the bulk solution. Alkali metal ions and chlorides interact with the protein surface, but such interactions are relatively weak and often transient. In this paper, computer simulations and analysis of protein structures are used to characterize the interactions between ions and the protein surface. The results show that the ion-binding properties of protein residues are highly variable. For example, alkali metal ions are more often associated with aspartate residues than with glutamates, whereas chlorides are most likely to be located near arginines. When comparing NaCl and KCl solutions, it was found that certain surface residues attract the anion more strongly in NaCl. This study demonstrates that protein–salt interactions should be accounted for in the planning and execution of experiments and simulations involving proteins, particularly if subtle structural details are sought after.
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| 8. |
- Friedman, Ran
(författare)
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Membrane-Ion Interactions
- 2018
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Ingår i: Journal of Membrane Biology. - : Springer. - 0022-2631 .- 1432-1424. ; 251:3, s. 453-460
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Tidskriftsartikel (refereegranskat)abstract
- Biomembranes assemble and operate at the interface with electrolyte solutions. Interactions between ions in solutions and the lipid affect the membrane structure, dynamics and electrostatic potential. In this article, I review some of the experimental and computational methods that are used to study membrane-ions interactions. Experimental methods that account for membrane-ion interactions directly and indirectly are presented first. Then, studies in which molecular dynamics simulations were used to gain an understanding of membrane-ion interactions are surveyed. Finally, the current view on membrane-ion interactions and their significance is briefly discussed.
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| 9. |
- Friedman, Ran
(författare)
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Preferential Binding of Lanthanides to Methanol Dehydrogenase Evaluated with Density Functional Theory
- 2021
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 125:9, s. 2251-2257
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Tidskriftsartikel (refereegranskat)abstract
- Methanol dehydrogenase (MDH) is an enzyme used by certain bacteria for the oxidation of methanol to formaldehyde, which is a necessary metabolic reaction. The discovery of a lanthanide-dependent MDH reveals that lanthanide ions (Ln(3+)) have a role in biology. Two types of MDH exist in methane-utilizing bacteria: one that is Ca2+-dependent (MxaF) and another that is Ln(3+)-dependent. Given that the triply charged Ln(3+) are strongly hydrated, it is not clear how preference for Ln(3+) is manifested and if the Ca2+-dependent MxaF protein can also bind Ln(3+) ions. A computational approach was used to estimate the Gibbs energy differences between the binding of Ln(3+) and Ca2+ to MDH using density functional theory. The results show that both proteins bind La3+ with higher affinity than Ca2+, albeit with a more pronounced difference in the case of Ln(3+)-dependent MDH. Interestingly, the binding of heavier lanthanides is preferred over the binding of La3+, with Gd3+ showing the highest affinity for both proteins of all Ln(3+) ions that were tested (La3+, Sm3+, Gd3+, Dy3+, and Lu3+). Energy decomposition analysis reveals that the higher affinity of La3+ than Ca2+ to MDH is due to stronger contributions of electrostatics and polarization, which overcome the high cost of desolvating the ion.
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| 10. |
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