Crowding Stabilizes DMSOâWater Hydrogen-Bonding Interactions

Subscriber access provided by UNIVERSITY OF ADELAIDE LIBRARIES

B: Liquids, Chemical and Dynamical Processes in Solution, Spectroscopy in Solution

Crowding Stabilizes DMSO – Water Hydrogen-Bonding Interactions Kwang-Im Oh, and Carlos R Baiz J. Phys. Chem. B, Just Accepted Manuscript • DOI: 10.1021/acs.jpcb.8b02739 • Publication Date (Web): 09 May 2018 Downloaded from http://pubs.acs.org on May 10, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 23 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The Journal of Physical Chemistry

Crowding Stabilizes DMSO – Water Hydrogenbonding Interactions Kwang-Im Oh+, Carlos R. Baiz*+ +Department of Chemistry, University of Texas at Austin, 105 E 24th St. Stop A5300 Austin, Texas 78712

ABSTRACT. Up to 40% of intracellular water is confined due to the dense packing of macromolecules, ions, and osmolytes. Despite the large body of work concerning the effect of additives on biomolecular structure and stability, the role of crowding and heterogeneity is not well understood. Here, infrared spectroscopy and molecular dynamics simulations are used to describe the mechanisms by which crowding modulates hydrogen bonding interactions between water and dimethyl sulfoxide (DMSO). Specifically, we use formamide and dimethylformamide (DMF) as molecular crowders and show that S=O hydrogen bond populations in aqueous mixtures are increased by both amides. These additives increase the amount of water within the DMSO first solvation shell through two mechanisms: a. directly stabilizing water-DMSO hydrogen bonds; b. increasing water exposure by destabilizing DMSO–DMSO self-interactions. Further, we quantified the hydrogen bond enthalpies between the different components: DMSO– water (61 kJ/mol) > DMSO–formamide (32 kJ/ mol) > water–water (23 kJ/mol) >> formamide– water (4.7 kJ/mol). Spectra of carbonyl stretching vibrations show that DMSO induces

ACS Paragon Plus Environment

1

The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 23

dehydration of amides as a result of strong DMSO–water interactions, which has been suggested as the main mechanism of protein destabilization.

Introduction Crowding and heterogeneity are hallmarks of biology at the molecular scale. The cell interior is densely packed; as much as 20-40% of intracellular water is confined by biomacromolecules or osmolytes.1-11 Crowding disrupts solvent hydrogen bond networks and modulates the hydration levels of proteins and osmolytes.12-17 Measuring these effects is challenging since a combination of structural sensitivity and chemical specificity is required. For these reasons, microscopic descriptions of complex mixtures, and the elements required to link solvent environments with biomolecular structure are not understood.18-21 Characterizing the effect of crowding on hydrogen bonding12,14-16,22 is the first step towards achieving a microscopic description of heterogeneous environments.23-26 Molecular dynamics (MD) simulations provide atomistic views of osmolyte or denaturant interactions12,18,27,28 and can predict protein stability semi-quantitatively.29-33 However, without direct experimental benchmarks, simulations can be subject to modeling bias.34-36 Building on our earlier work37 in which we measured dimethyl sulfoxide (DMSO)-water hydrogen bond populations, here we investigate the effects of small amides, as molecular crowders and simple amino-acid analogs. We show that crowding stabilizes hydrogen bonds in aqueous DMSO, a common denaturant,

38-40

cryoprotectant,41 and drug permeation agent.42

Specifically, we map hydrogen bond populations of the S=O and C=O groups in DMSO/water/formamide or dimethylformamide (DMF) ternary mixtures using infrared


2

Page 3 of 23 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


spectroscopy. The sensitivities of S=O37,43 and C=O44-47 stretching vibrations to the local electrostatic environment enabled us to quantify the thermodynamics of hydrogen bonding. Populations were extracted from the S=O and C=O absorption lineshapes, and an atomistic interpretation was achieved by comparing the experimental populations with MD simulations of the same mixtures. Formamide and DMF both increase DMSO–water hydrogen bond populations. Despite differences in polarity, the effects are similar for both amides. In addition, we measured hydrogen bond thermodynamics between all components in the mixtures. The results show that DMSO–water, DMSO–formamide, and water–water interactions are stronger than interactions between water and amides. We selected formamide and DMF as model systems to explore the effects of hydrogen bond donating ability and bulk polarity in ternary mixtures.

48,49

Given their chemical structure and

properties, these amides can be considered minimal models of the protein backbone that have limited chemical complexity and few conformational degrees of freedom. Proteins can change conformation or aggregate in the presence of osmolytes, which may bury or expose polar groups, thus alter the donor/acceptor balance. Conformation-dependent effects, combined with slow structural dynamics, make attempts at establishing relationships between protein structure and solvation shell composition particularly challenging.16,19,35,50-55 These studies are a first step towards bridging the knowledge gap between solvent composition and biomolecular structure, dynamics, and stability. Methods Herein, we provide an outline of experimental procedures and theoretical methods. Details are provided in the Supporting Information.


3


Page 4 of 23

FTIR spectroscopy: FTIR measurements were performed with 1 cm-1 resolution using a pair of CaF2 windows. The path length was varied depending on the concentration in order to keep the optical densities within the linear range of the FTIR spectrometer. All chemicals were used as received. Quantum Mechanical calculations: To assign peak frequencies, geometry optimization was performed on putative starting structures using B3LYP/6-31G(d) level, then further optimization and frequency analysis were carried out at the MP2/cc-PVZ level of theory. MD simulations and H-bond analysis: Simulations of DMSO/water binary mixtures, formamide/DMSO/water ternary mixtures, and DMF/DMSO/water ternary mixtures at varying concentrations were carried out with CHARMM General Force-field (CGenFF).56 All simulations were performed using the GROMACS 5.12 package.57 Hydrogen bond populations were computed using a 3.5 Å donor (D) to acceptor (A) distance cutoff, between oxygen atoms of donor and acceptor, and a 30 ° D-H-A angle cutoff. The distance parameter was selected to match the first minimum of the Donor-Acceptor radial distribution function. Results and Discussion Vibrational Line Shapes. Figure 1 shows S=O and C=O stretching band spectra at low (1 mol%), medium (50 mol%), and high DMSO (100 mol%) concentrations. Both vibrational modes are sensitive reporters of their immediate hydrogen bond environments. We have previously decomposed the S=O stretching lineshape into non-hydrogen bonded (0HB), singly hydrogen-bonded (1HB), and doubly hydrogen-bonded (2HB), peaks and have quantified the populations over the entire DMSO/water concentration range.37 Non-hydrogen bonded species include isolated (“Free”) and self-associated DMSO dimers (“Aggregate or Agg”). The S=O and C=O peaks gradually blue shift with increasing DMSO concentrations (see SI Section1,


4

Page 5 of 23 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Section2, and Figure S1) as hydrogen-bond populations decrease with increasing DMSO concentrations. Figures 1A and S1 show the S=O absorption spectrum within three DMSO concentration regimes in the ternary mixtures. Spectra blue-shift at higher DMSO concentrations as a result of lower S=O H-bond populations. Spectra with formamide or DMF are very similar, except at higher concentrations, which exhibit larger differences. Since the two amides differ in molecular volume and molecular mass, we have chosen to keep the amount of additive constant at 15% w/v to study crowding effects. Formamide and DMF have a different balance of donor/acceptor groups. Formamide can donate two hydrogen bonds through its -NH2 group and accept two hydrogen bonds through its carbonyl. DMF, on the other hand, can only accept two hydrogen bonds. The C=O stretching bands of formamide and DMF serve as additional reporters on the solution environment (Figure 1B, Figure S2). Spectra show blue-shifted lineshapes at higher DMSO concentrations. Formamide and DMF peaks are broad at low concentrations, as the groups are highly solvated. Narrower peaks at higher DMSO concentrations are a result of more uniform 0HB environments. Compared to formamide, DMF shows narrower peaks and smaller spectral shifts, indicating weaker C=O hydrogen bonds. Despite formamide’s ability to donate hydrogen bonds, our electronic structure computations show that hydrogen bonding with the -NH2 group produces only small shifts in the C=O frequencies compared to direct bonding with the C=O. (See SI Section3 and Figure S3). Hydrogen-bond Populations. Quantitative H-bond populations were extracted from the spectra by fitting the lineshapes to individual peaks. The fits were highly constrained based on several criteria described previously.37 In brief, spectra were fit to a combination of six Gaussian


5


Page 6 of 23

profiles and populations extracted from the relative peak areas as described in the Supporting Information (Section 4). While the spectral lineshapes of these heterogeneous mixtures are complex and contain several features, including some CH3 bend peaks, we find that a combination of Gaussians reproduces the measured spectra, and their second derivatives, very well, particularly at low and intermediate DMSO concentrations water–water >> formamide–water (Table 1). These studies revealed that formamide–DMSO energies are significantly stronger than formamide–water, suggesting that direct interactions with DMSO can be an important contribution towards increasing the availability of water molecules in the solvent. Our results provide a molecular-level description of crowding effects on solvent environments and may be used as a basis for understanding cryoprotectant toxicity in cells and tissues, since toxicity has been correlated with the number of hydrogen bond donors and acceptors.70 For these reasons, further fundamental studies are required to construct a molecular foundation for understanding the complex biological effects of these small molecules.


11


Page 12 of 23

FIGURES.

Figure 1. (A) DMSO infrared absorption spectra in the S=O stretching region. (B) C=O stretching band of formamide (or DMF) in varying DMSO/water mixtures. Concentrationdependent spectra were measured at following concentrations: 15 %w/v formamide (6.5 mol%) or DMF (4.1 mol%) in low (1 mol%), medium (50 mol%) and high (100 mol%) DMSO/D2O mixtures. Final concentrations of DMSO with formamide (or DMF) are 0.93 mol% (0.96 mol%), 43 mol% (45 mol%), and 79 mol% (86 mol%) indicated by red, green, and blue, respectively. Solid and dashed lines indicate DMSO/water solutions with formamide and DMF, respectively.


12

Page 13 of 23 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 2. Hydrogen bond populations surrounding the S=O group in DMSO/water binary (red), formamide/DMSO/water (blue), and DMF/DMSO/water (black) ternary mixtures across the entire DMSO concentration range. The curves are comparisons between varying mixtures to (A) 2HB, (B) 1HB, (C) DMSO dimers (“Agg”) and (D) “Free”, see also Figure S4. The three observed concentration regimes are labeled “water rich” (0-10 mol%), “crowding” (10-75 mol%) and “DMSO rich” (75-90%). The arrows indicate changes from binary mixtures to ternary mixtures (blue: formamide/DMSO/water, and gray: DMF/DMSO/water).


13


Page 14 of 23

Figure 3. Predicted hydrogen bond ensemble populations from MD simulations, plotted as a function of the DMSO mole fraction. Three HB ensemble populations surrounding the S=O group are described in (A) DMSO/water, (B) DMSO/water/formamide, (C) DMSO/water/DMF, and (D) DMSO/water/formamide with DMSO–formamide and DMSO–formamide DMSO– water interactions. DMSO–water interactions are plotted as closed circles, while DMSO– formamide (DMSO – water/formamide) interactions are described as open circles (triangles). Three HB populations are indicated by different colors.


14

Page 15 of 23 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 4. Analysis of molecular dynamics trajectories: (A) Radial distribution functions surrounding DMSO in the mixtures. Solid and dashed lines indicate DMSO–water and DMSO– amide interactions, respectively. (B) Relative number of molecules in first solvation shell of DMSO. Closed and open circles represent DMSO–water and DMSO–amide interactions.


15


Page 16 of 23

Figure 5. (A) Experimental H-bond enthalpies (∆H) and entropies (T∆S at 298.15 K) determined by temperature-dependent FTIR spectroscopy. Error bars represent the fitting uncertainties (Figure S13). *Water–water interactions are from the literature.66 Details of the methods and analyses are provided in the SI Section 6. (B) Average number of H-bonds accepted by formamide (FA) binary mixtures with water, and formamide/water/DMSO ternary mixtures with a constant 17.5 mol% DMSO concentration.


16

Page 17 of 23 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


TABLES. Table 1. Enthalpies and entropies were extracted from temperature-dependent hydrogen bond populations as described in the text. Interaction

Enthalpy

Entropy at 298.15 K

(∆H, kJ/mol)

(T∆S, kJ/mol)

water–DMSO

61.1 ± 13.3

62.6 ± 13.3

formamide–DMSO

31.5 ± 5.40

26.5 ± 5.07

water–water

23.3

11.0

DMSO–DMSO

7.93 ± 0.70

11.5 ± 0.69

formamide–water

4.66 ± 0.65

0.66 ± 0.64

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected] Author Contributions C.B and K-I. O. designed the research. K-I. O. performed the experiments. C.B. and K-I. O. analyzed the results and wrote the manuscript. Funding Sources We gratefully acknowledge a research grant from the Welch Foundation (F-1891). Notes


17


Page 18 of 23

The authors declare no competing financial interest. ACKNOWLEDGMENT This is a Plan II SAWIAGOS Project. Computer simulations were carried out using the Texas Advanced Computing Center (TACC) resources. ASSOCIATED CONTENT Supporting Information. The supporting information includes: 1. Experimental procedures including sample preparation and IR measurements. 2. Lineshape analysis and extraction of Hbond populations from IR spectra. 3. Vibrational frequencies derived from quantum mechanical calculations 4. MD simulation protocols and analysis of results. 5. Additional figures referenced in the text. This information is available free of charge via the Internet at http://pubs.acs.org REFERENCES (1)

Ellis, R. J. Macromolecular Crowding: An Important but Neglected Aspect of the Intracellular Environment. Curr. Opin. Struct. Biol. 2001, 11, 500. (2) Ellis, R. J.; Minton, A. P. Join the Crowd. Nature 2003, 425, 27-28. (3) Gnutt, D.; Gao, M.; Brylski, O.; Heyden, M.; Ebbinghaus, S. Excluded-volume Effects in Living Cells. Angew. Chem. Int. Ed. Engl. 2015, 54, 2548-2551. (4) Kuznetsova, I. M.; Turoverov, K. K.; Uversky, V. N. What Macromolecular Crowding Can Do to a Protein. Int. J. Mol. Sci. 2014, 15, 23090-23140. (5) Minton, A. P. The Influence of Macromolecular Crowding and Macromolecular Confinement on Biochemical Reactions in Physiological Media. J. Biol. Chem. 2001, 276, 10577-10580. (6) Rivas, G.; Minton, A. P. Macromolecular Crowding In Vitro, In Vivo, and In Between. Trends Biochem. Sci. 2016, 41, 970-981. (7) Sharp, K. A. Unpacking the Origins of In-cell Crowding. Proc. Natl. Acad. Sci. U.S.A. 2016, 113, 1684-1685. (8) Tan, C.; Saurabh, S.; Bruchez, M. P.; Nature, R. S. Molecular Crowding Shapes Gene Expression in Synthetic Cellular Nanosystems. Nat. Nanotechnol. 2013, 8, 602-608. (9) Van Horn, W. D.; Ogilvie, M. E.; Flynn, P. F. Reverse Micelle Encapsulation as a Model for Intracellular Crowding. J. Am. Chem. Soc. 2009, 131, 8030-8039. (10) Yu, H.; Rathore, S. S.; Shen, C.; Liu, Y.; Ouyang, Y.; Stowell, M. H.; Shen, J. Reconstituting Intracellular Vesicle Fusion Reactions: The Essential Role of Macromolecular Crowding. J. Am. Chem. Soc. 2015, 137, 12873-12883.


18

Page 19 of 23 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(11) Tros, M.; Zheng, L.; Hunger, J.; Bonn, M.; Bonn, D.; Smits, G. J.; Woutersen, S. Picosecond Orientational Dynamics of Water in Living Cells. Nat. Commun. 2017, 8, 904. (12) Harada, R.; Sugita, Y.; Feig, M. Protein Crowding Affects Hydration Structure and Dynamics. J. Am. Chem. Soc. 2012, 134, 4842-4849. (13) Kundu, A.; Verma, P. K.; Cho, M. Effect of Osmolytes on the Conformational Behavior of a Macromolecule in a Cytoplasm-like Crowded Environment: A Femtosecond Mid-IR Pump-Probe Spectroscopy Study. J. Phys. Chem. Lett. 2018, 724-731. (14) Samanta, N.; Luong, T. Q.; Das Mahanta, D.; Mitra, R. K.; Havenith, M. Effect of Short Chain Poly(ethylene glycol)s on the Hydration Structure and Dynamics around Human Serum Albumin. Langmuir 2016, 32, 831-837. (15) Senske, M.; Törk, L.; Born, B.; Havenith, M.; Herrmann, C.; Ebbinghaus, S. Protein Stabilization by Macromolecular Crowding Through Enthalpy Rather than Entropy. J. Am. Chem. Soc. 2014, 136, 9036-9041. (16) White, D. A.; Buell, A. K.; Knowles, T. P. J.; Welland, M. E.; Dobson, C. M. Protein Aggregation in Crowded Environments. J. Am. Chem. Soc. 2010, 132, 5170-5175. (17) Wang, Y.; Sarkar, M.; Smith, A. E.; Krois, A. S.; Pielak, G. J. Macromolecular Crowding and Protein Stability. J. Am. Chem. Soc. 2012, 134, 16614-16618. (18) Bellissent-Funel, M.-C.; Hassanali, A.; Havenith, M.; Henchman, R.; Pohl, P.; Sterpone, F.; van der Spoel, D.; Xu, Y.; García, A. E. Water Determines the Structure and Dynamics of Proteins. Chem. Rev. 2016, 116, 7673-7697. (19) England, J. L.; Haran, G. Role of Solvation Effects in Protein Denaturation: From Thermodynamics to Single Molecules and Back. Annu. Rev. Phys. Chem. 2011, 62, 257277. (20) Govrin, R.; Schlesinger, I.; Tcherner, S.; Sivan, U. Regulation of Surface Charge by Biological Osmolytes. J. Am. Chem. Soc. 2017, 139, 15013-15021. (21) Jensen, M. R.; Zweckstetter, M.; Huang, J.-r.; Blackledge, M. Exploring Free-energy Landscapes of Intrinsically Disordered Proteins at Atomic Resolution Using NMR Spectroscopy. Chem. Rev. 2014, 114, 6632-6660. (22) Verma, P. K.; Kundu, A.; Ha, J.-H.; Cho, M. Water Dynamics in Cytoplasm-Like Crowded Environment Correlates with the Conformational Transition of the Macromolecular Crowder. J. Am. Chem. Soc. 2016, 138, 16081-16088. (23) Murray, B.; Rosenthal, J.; Zheng, Z.; Isaacson, D.; Zhu, Y.; Belfort, G. Cosolute Effects on Amyloid Aggregation in a Nondiffusion Limited Regime: Intrinsic Osmolyte Properties and the Volume Exclusion Principle. Langmuir 2015, 31, 4246-4254. (24) Politou, A.; Temussi, P. A. Revisiting a Dogma: The Effect of Volume Exclusion in Molecular Crowding. Curr. Opin. Struct. Biol. 2015, 30, 1-6. (25) Senske, M.; Smith, A. E.; Pielak, G. J. Protein Stability in Reverse Micelles. Angew. Chem. Int. Ed. Engl. 2016, 55, 3586-3589. (26) Sharp, K. A. Analysis of the Size Dependence of Macromolecular Crowding Shows That Smaller Is Better. Proc. Natl. Acad. Sci. U.S.A. 2015, 112, 7990-7995. (27) Camilloni, C.; Rocco, A. G.; Eberini, I.; Gianazza, E.; Broglia, R. A.; Tiana, G. Urea and Guanidinium Chloride Denature Protein L in Different Ways in Molecular Dynamics Simulations. Biophys. J. 2008, 94, 4654-4661. (28) Mountain, R. D.; Thirumalai, D. Molecular Dynamics Simulations of End-to-End Contact Formation in Hydrocarbon Chains in Water and Aqueous Urea Solution. J. Am. Chem. Soc. 2003, 125, 1950-1957.


19


Page 20 of 23

(29) O'Brien, E. P.; Ziv, G.; Haran, G.; Brooks, B. R.; Thirumalai, D. Effects of Denaturants and Osmolytes on Proteins Are Accurately Predicted by the Molecular Transfer Model. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 13403-13408. (30) Schuler, B.; Lipman, E. A.; Eaton, W. A. Probing the Free-energy Surface for Protein Folding with Single-molecule Fluorescence Spectroscopy. Nature 2002, 419, 743-747. (31) Thirumalai, D.; O'Brien, E. P.; Morrison, G.; Hyeon, C. Theoretical Perspectives on Protein Folding. Annu. Rev. Biophys. 2010, 39, 159-183. (32) Timasheff, S. N. The Control of Protein Stability and Association by Weak Interactions with Water: How Do Solvents Affect These Processes? Annu. Rev. Biophys. Biomol. Struct. 1993, 22, 67-97. (33) Ziv, G.; Haran, G. Protein Folding, Protein Collapse, and Tanford's Transfer Model: Lessons from Single-molecule FRET. J. Am. Chem. Soc. 2009, 131, 2942-2947. (34) Piana, S.; Klepeis, J. L.; Shaw, D. E. Assessing the Accuracy of Physical Models Used in Protein-folding Simulations: Quantitative Evidence from Long Molecular Dynamics Simulations. Curr. Opin. Struct. Biol. 2014, 24, 98-105. (35) Piana, S.; Lindorff-Larsen, K.; Shaw, D. E. How Robust Are Protein Folding Simulations with Respect to Force Field Parameterization? Biophys. J. 2011, 100, L47-L49. (36) Prabhu, N.; Sharp, K. Protein-solvent Interactions. Chem. Rev. 2006, 106, 1616-1623. (37) Oh, K.-I.; Rajesh, K.; Stanton, J. F.; Baiz, C. R. Quantifying Hydrogen-Bond Populations in Dimethyl Sulfoxide/Water Mixtures. Angew. Chem. Int. Ed. Engl. 2017, 56, 1137511379. (38) Batista, A. N. L.; Batista, J. M.; Bolzani, V. S.; Furlan, M.; Blanch, E. W. Selective DMSO-induced Conformational Changes in Proteins from Raman Optical Activity. Phys. Chem. Chem. Phys. 2013, 15, 20147-20152. (39) Kim, K. R.; Kwon, D. Y.; Yoon, S. H.; Kim, W. Y.; Kim, K. H. Purification, Refolding, and Characterization of Recombinant Pseudomonas Fluorescens Lipase. Protein Expr. Purif. 2005, 39, 124-129. (40) Voets, I. K.; Cruz, W. A.; Moitzi, C.; Lindner, P.; Arêas, E. P. G.; Schurtenberger, P. DMSO-Induced Denaturation of Hen Egg White Lysozyme. J. Phys. Chem. B 2010, 114, 11875-11883. (41) Wang, X.; Hua, T.-C.; Sun, D.-W.; Liu, B.; Yang, G.; Cao, Y. Cryopreservation of Tissueengineered Dermal Replacement in Me2SO: Toxicity Study and Effects of Concentration and Cooling Rates on Cell Viability. Cryobiology 2007, 55, 60-65. (42) Liong, M.; Lu, J.; Kovochich, M.; Xia, T.; Ruehm, S. G.; Nel, A. E.; Tamanoi, F.; Zink, J. I. Multifunctional Inorganic Nanoparticles for Imaging, Targeting, and Drug Delivery. ACS Nano 2008, 2, 889-896. (43) Fawcett, W. R.; Kloss, A. A. Solvent-induced Frequency Shifts in the Infrared Spectrum of Dimethyl Sulfoxide in Organic Solvents. J. Phys. Chem. 1996, 100, 2019-2024. (44) Fried, S. D.; Bagchi, S.; Boxer, S. G. Extreme Electric Fields Power Catalysis in the Active Site of Ketosteroid Isomerase. Science 2014, 346, 1510-1514. (45) Kim, H.; Cho, M. Infrared Probes for Studying the Structure and Dynamics of Biomolecules. Chem. Rev. 2013, 113, 5817-5847. (46) Oh, K.-I.; Fiorin, G.; Gai, F. How Sensitive is the Amide I Vibration of the Polypeptide Backbone to Electric Fields? ChemPhysChem 2015, 16, 3595-3598. (47) Reppert, M.; Tokmakoff, A. Computational Amide I 2D IR Spectroscopy as a Probe of Protein Structure and Dynamics. Annu. Rev. Phys. Chem. 2016, 67, 359-386.


20

Page 21 of 23 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(48) Chang, Y. J.; Castner, E. W. Femtosecond Dynamics of Hydrogen-Bonding Solvents Formamide and N-Methylformamide in Acetonitrile, DMF, and Water. J. Chem. Phys. 1993, 99, 113-125. (49) Kamlet, M. J.; Abboud, J. L. M.; Abraham, M. H.; Taft, R. W. Linear Solvation Energy Relationships. 23. A Comprehensive Collection of the Solvatochromic Parameters, .Pi.*, .Alpha., and .Beta., and Some Methods for Simplifying the Generalized Solvatochromic Equation. J. Org. Chem. 1983, 48, 2877-2887. (50) Hummer, G.; Garde, S.; García, A. E.; Paulaitis, M. E.; Pratt, L. R. The Pressure Dependence of Hydrophobic Interactions Is Consistent with the Observed Pressure Denaturation of Proteins. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 1552-1555. (51) Jas, G. S.; Rentchler, E. C.; Słowicka, A. M.; Hermansen, J. R.; Johnson, C. K.; Middaugh, C. R.; Kuczera, K. Reorientation Motion and Preferential Interactions of a Peptide in Denaturants and Osmolyte. J. Phys. Chem. B 2016, 120, 3089-3099. (52) Stirnemann, G.; Kang, S.-g.; Zhou, R.; Berne, B. J. How Force Unfolding Differs from Chemical Denaturation. Proc. Natl. Acad. Sci. U.S.A. 2014, 111, 3413-3418. (53) Klepeis, J. L.; Lindorff-Larsen, K.; Dror, R. O.; Shaw, D. E. Long-timescale Molecular Dynamics Simulations of Protein Structure and Function. Curr. Opin. Struct. Biol. 2009, 19, 120-127. (54) Onufriev, A.; Bashford, D.; Case, D. A. Exploring Protein Native States and Large-scale Conformational Changes with a Modified Generalized Born Model. Proteins 2004, 55, 383-394. (55) Shaw, D. E.; Maragakis, P.; Lindorff-Larsen, K.; Piana, S.; Dror, R. O.; Eastwood, M. P.; Bank, J. A.; Jumper, J. M.; Salmon, J. K.; Shan, Y.et al. Atomic-level Characterization of the Structural Dynamics of Proteins. Science 2010, 330, 341-346. (56) Vanommeslaeghe, K.; Hatcher, E.; Acharya, C.; Kundu, S.; Zhong, S.; Shim, J.; Darian, E.; Guvench, O.; Lopes, P.; Vorobyov, I.et al. CHARMM General Force Field: A Force Field for Drug-like Molecules Compatible with the CHARMM All-atom Additive Biological Force Fields. J. Comput. Chem. 2010, 31, 671-690. (57) Abraham, M. J.; Murtola, T.; Schulz, R.; Páll, S.; Smith, J. C. GROMACS: High Performance Molecular Simulations Through Multi-level Parallelism from Laptops to Supercomputers. SoftwareX 2015, 1-2, 19-25. (58) Stumpe, M. C.; Grubmüller, H. Aqueous Urea Solutions: Structure, Energetics, and Urea Aggregation. J. Phys. Chem. B 2007, 111, 6220-6228. (59) Ghosal, S.; Hemminger, J. C.; Bluhm, H.; Mun, B. S.; Hebenstreit, E. L. D.; Ketteler, G.; Ogletree, D. F.; Requejo, F. G.; Salmeron, M. Electron Spectroscopy of Aqueous Solution Interfaces Reveals Surface Enhancement of Halides. Science 2005, 307, 563-566. (60) Idrissi, A.; Marekha, B. A.; Barj, M.; Miannay, F. A.; Takamuku, T.; Raptis, V.; Samios, J.; Jedlovszky, P. Local Structure of Dilute Aqueous DMSO Solutions, As Seen From Molecular Dynamics Simulations. J. Chem. Phys. 2017, 146, 234507. (61) Horn, H. W.; Swope, W. C.; Pitera, J. W.; Madura, J. D.; Dick, T. J.; Hura, G. L.; HeadGordon, T. Development of an Improved Four-site Water Model for Biomolecular Simulations: TIP4P-Ew. J. Chem. Phys. 2004, 120, 9665-9678. (62) Kiefer, J.; Noack, K.; Kirchner, B. Hydrogen Bonding in Mixtures of Dimethyl Sulfoxide and Cosolvents. Curr. Phys. Chem. 2011. (63) LeBel, R. G.; Goring, D. A. I. Density, Viscosity, Refractive Index, and Hygroscopicity of Mixtures of Water and Dimethyl Sulfoxide. J. Chem. Eng. Data 1962, 7, 100-101.


21


Page 22 of 23

(64) Kirchner, B.; Reiher, M. The Secret of Dimethyl Sulfoxide-water Mixtures. A Quantum Chemical Study of 1DMSO-nWater Clusters. J. Am. Chem. Soc. 2002, 124, 6206-6215. (65) Klopper, W.; Luthi, H. P. The MP2 Limit Correction Applied to Coupled Cluster Calculations of the Electronic Dissociation Energies of the Hydrogen Fluoride and Water Dimers. Mol. Phys. 1999, 96, 559-570. (66) Suresh, S. J.; Naik, V. M. Hydrogen Bond Thermodynamic Properties of Water from Dielectric Constant Data. J. Chem. Phys. 2000, 113, 9727-9732. (67) Ding, B.; Mukherjee, D.; the, Chen, J.; Gai, F. Do Guanidinium and Tetrapropylammonium Ions Specifically Interact with Aromatic Amino Acid Side Chains? Proc. Natl. Acad. Sci. U.S.A. 2017, 114, 1003-1008. (68) Sarma, R.; Paul, S. Exploring the Molecular Mechanism of Trimethylamine-n-oxide's Ability to Counteract the Protein Denaturing Effects of Urea. J. Phys. Chem. B 2013, 117, 5691-5704. (69) Street, T. O.; Bolen, D. W.; Rose, G. D. A Molecular Mechanism for Osmolyte-induced Protein Stability. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 13997-14002. (70) Fahy, G. M. Cryoprotectant Toxicity Neutralization. Cryobiology 2010, 60, S45-53. (71) Best, B. P. Cryoprotectant Toxicity: Facts, Issues, and Questions. Rejuvenation Res. 2015, 18, 422-436.


22

Page 23 of 23 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


BRIEFS. Crowding and dehydration: Infrared spectra of DMSO and amide mixtures suggest that crowding strengthens DMSO – water hydrogen bonding interactions.

TOC Graphic


23

Crowding Stabilizes DMSOâWater Hydrogen-Bonding Interactions

Recommend Documents

Crowding Stabilizes DMSOâWater Hydrogen-Bonding Interactions