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Vibrational Probes of Biomolecular Structure and Dynamics

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Published Papers

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Physical Chemistry".

Deadline for manuscript submissions: closed (15 February 2019) | Viewed by 55847

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Special Issue Editor

Prof. Dr. Chong Fang

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Guest Editor

Department of Chemistry, Oregon State University, Corvallis, OR 97331, USA
Interests: fluorescent proteins; biosensors; chemosensors; photoswitchable and photoconvertible fluorescent proteins; femtosecond-stimulated Raman; transient absorption; excited-state dynamics; fluorogenicity; redder probes; rational protein design; battery electrolytes; materials characterization
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Special Issue Information

Dear Colleagues,

The past few decades have seen tremendous progress in understanding the structure–function relationships of biomolecular systems from microscopic motions to macroscopic properties. Among all the molecular characterization methods, vibrational probes stand out as a versatile and fruitful endeavor because they are highly sensitive to local environment and can be designed, modified, positioned, and controlled to reveal previously unavailable, unknown, or unattainable information about the system under investigation.

The vibrational probes used for steady-state biomolecular structural determination include functional groups and chemical compounds such as carbonyl, nitrile, azide, and cyanamide, while the time-resolved studies can use those characteristic probes to track equilibrium processes (e.g., anharmonic coupling, H-bonding interactions, spectral diffusion, chemical exchange, energy transport) and non-equilibrium processes (e.g., protein folding and unfolding, cooling, electron and proton transfer, transient absorption, fluorescence). Such a wealth of information has been obtained by active researchers across the modern disciplines of physical chemistry and chemical physics, biophysics and biochemistry, ultrafast spectroscopy and nonlinear optics, chemical biology, imaging and microscopy. Individual or pairs of isotopically labeled, engineered or non-natural probes, in conjunction with various advanced spectroscopic and microscopic techniques based on light-matter interactions, have further expanded the repertoire of vibrational toolset.

The aim of this Special Issue is to bring together leading experts across disciplines and highlight recent advances utilizing vibrational probes to study biomolecular structure and dynamics. Both original research articles and reviews are welcome, and articles that report or propose new ideas and new directions to stimulate future development and applications are particularly welcome.

Prof. Dr. Chong Fang
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

structure-function relationships
molecular spectroscopy
imaging and microscopy
protein engineering
bioprobe development
potential energy surface
vibrational dynamics
functional motions and interactions
equilibrium and non-equilibrium processes

Published Papers (12 papers)

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Research

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11 pages, 2441 KiB

Open AccessArticle

Isonitrile-Derivatized Indole as an Infrared Probe for Hydrogen-Bonding Environments

by Min You, Liang Zhou, Xinyue Huang, Yang Wang and Wenkai Zhang

Molecules 2019, 24(7), 1379; https://doi.org/10.3390/molecules24071379 - 08 Apr 2019

Cited by 11 | Viewed by 2691

Abstract

The isonitrile (NC) group has been shown to be a promising infrared probe for studying the structure and dynamics of biomolecules. However, there have been no systematic studies performed on the NC group as an infrared probe, when it is bonded to an indole ring. Here, we systematically study the NC stretching mode of two model compounds, 5-isocyano-1H-indole (5ICI) and 5-isocyano-1-methyl-1H-indole (NM5ICI), using Fourier transform infrared (FTIR) spectroscopy. The NC stretching frequency is shown to be strongly dependent on the polarizability of protic solvents and the density of hydrogen-bond donor groups in the solvent when NC is bonded to an indole ring. Infrared pump–probe studies of 5ICI in DMSO and in EtOH further support that the NC stretching mode could be used as a site-specific infrared probe for local environments when NC is bonded to an indole ring. Full article

(This article belongs to the Special Issue Vibrational Probes of Biomolecular Structure and Dynamics)

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15 pages, 1667 KiB

Open AccessFeature PaperArticle

Excited State Frequencies of Chlorophyll f and Chlorophyll a and Evaluation of Displacement through Franck-Condon Progression Calculations

by Noura Zamzam and Jasper J. van Thor

Molecules 2019, 24(7), 1326; https://doi.org/10.3390/molecules24071326 - 04 Apr 2019

Cited by 11 | Viewed by 3103

Abstract

We present ground and excited state frequency calculations of the recently discovered extremely red-shifted chlorophyll f. We discuss the experimentally available vibrational mode assignments of chlorophyll f and chlorophyll a which are characterised by particularly large downshifts of 13¹-keto mode in the excited state. The accuracy of excited state frequencies and their displacements are evaluated by the construction of Franck–Condon (FC) and Herzberg–Teller (HT) progressions at the CAM-B3LYP/6-31G(d) level. Results show that while CAM-B3LYP results are improved relative to B3LYP calculations, the displacements and downshifts of high-frequency modes are underestimated still, and that the progressions calculated for low temperature are dominated by low-frequency modes rather than fingerprint modes that are Resonant Raman active. Full article

(This article belongs to the Special Issue Vibrational Probes of Biomolecular Structure and Dynamics)

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10 pages, 1284 KiB

Open AccessArticle

Ethylene Measurements from Sweet Fruits Flowers Using Photoacoustic Spectroscopy

by Cristina Popa

Molecules 2019, 24(6), 1144; https://doi.org/10.3390/molecules24061144 - 22 Mar 2019

Cited by 19 | Viewed by 3209

Abstract

Ethylene is a classical plant hormone and has appeared as a strong molecule managing many physiological and morphological reactions during the life of a plant. With laser-based photoacoustic spectroscopy, ethylene can be identified with high sensitivity, at a high rate and with very good selectivity. This research presents the dynamics of trace gases molecules for ethylene released by cherry flowers, apple flowers and strawberry flowers. The responses of distinctive organs to ethylene may fluctuate, depending on tissue sensitivity and the phase of plant development. From the determinations of this study, the ethylene molecules at the flowers in the nitrogen flow were established in lower concentrations when the value is correlated to the ethylene molecules at the flowers in synthetic air flow. Full article

(This article belongs to the Special Issue Vibrational Probes of Biomolecular Structure and Dynamics)

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27 pages, 11051 KiB

Open AccessArticle

DFT Computed Dielectric Response and THz Spectra of Organic Co-Crystals and Their Constituent Components

by Joseph W. Bennett, Michaella E. Raglione, Shalisa M. Oburn, Leonard R. MacGillivray, Mark A. Arnold and Sara E. Mason

Molecules 2019, 24(5), 959; https://doi.org/10.3390/molecules24050959 - 08 Mar 2019

Cited by 4 | Viewed by 4957

Abstract

Terahertz (THz) spectroscopy has been put forth as a non-contact, analytical probe to characterize the intermolecular interactions of biologically active molecules, specifically as a way to understand, better develop, and use active pharmaceutical ingredients. An obstacle towards fully utilizing this technique as a probe is the need to couple features in the THz regions to specific vibrational modes and interactions. One solution is to use density functional theory (DFT) methods to assign specific vibrational modes to signals in the THz region, coupling atomistic insights to spectral features. Here, we use open source planewave DFT packages that employ ultrasoft pseudopotentials to assess the infrared (IR) response of organic compounds and complex co-crystal formulations in the solid state, with and without dispersion corrections. We compare our DFT computed lattice parameters and vibrational modes to experiment and comment on how to improve the agreement between theory and modeling to allow for THz spectroscopy to be used as an analytical probe in complex biologically relevant systems. Full article

(This article belongs to the Special Issue Vibrational Probes of Biomolecular Structure and Dynamics)

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15 pages, 4186 KiB

Open AccessArticle

Differentiation between Enamines and Tautomerizable Imines Oxidation Reaction Mechanism using Electron-Vibration-Vibration Two Dimensional Infrared Spectroscopy

by Fengqin Long, Zheng Chen, Keli Han, Lu Zhang and Wei Zhuang

Molecules 2019, 24(5), 869; https://doi.org/10.3390/molecules24050869 - 01 Mar 2019

Cited by 6 | Viewed by 3402

Abstract

Intermediates lie at the center of chemical reaction mechanisms. However, detecting intermediates in an organic reaction and understanding its role in reaction mechanisms remains a big challenge. In this paper, we used the theoretical calculations to explore the potential of the electron-vibration-vibration two-dimensional infrared (EVV-2DIR) spectroscopy in detecting the intermediates in the oxidation reactions of enamines and tautomerizable imines with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). We show that while it is difficult to identify the intermediates from their infrared and Raman signals, the simulated EVV-2DIR spectra of these intermediates have well resolved spectral features, which are absent in the signals of reactants and products. These characteristic spectral signatures can, therefore, be used to reveal the reaction mechanism as well as monitor the reaction progress. Our work suggests the potential strength of EVV-2DIR technique in studying the molecular mechanism of organic reactions in general. Full article

(This article belongs to the Special Issue Vibrational Probes of Biomolecular Structure and Dynamics)

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12 pages, 2864 KiB

Open AccessArticle

4-Cyanoindole-2′-deoxyribonucleoside as a Dual Fluorescence and Infrared Probe of DNA Structure and Dynamics

by Ismail A. Ahmed, Arusha Acharyya, Christina M. Eng, Jeffrey M. Rodgers, William F. DeGrado, Hyunil Jo and Feng Gai

Molecules 2019, 24(3), 602; https://doi.org/10.3390/molecules24030602 - 08 Feb 2019

Cited by 7 | Viewed by 3982

Abstract

Unnatural nucleosides possessing unique spectroscopic properties that mimic natural nucleobases in both size and chemical structure are ideally suited for spectroscopic measurements of DNA/RNA structure and dynamics in a site-specific manner. However, such unnatural nucleosides are scarce, which prompts us to explore the utility of a recently found unnatural nucleoside, 4-cyanoindole-2′-deoxyribonucleoside (4CNI-NS), as a site-specific spectroscopic probe of DNA. A recent study revealed that 4CNI-NS is a universal nucleobase that maintains the high fluorescence quantum yield of 4-cyanoindole and that among the four natural nucleobases, only guanine can significantly quench its fluorescence. Herein, we further show that the C≡N stretching frequency of 4CNI-NS is sensitive to the local environment, making it a useful site-specific infrared probe of oligonucleotides. In addition, we demonstrate that the fluorescence-quencher pair formed by 4CNI-NS and guanine can be used to quantitatively assess the binding affinity of a single-stranded DNA to the protein system of interest via fluorescence spectroscopy, among other applications. We believe that this fluorescence binding assay is especially useful as its potentiality allows high-throughput screening of DNA–protein interactions. Full article

(This article belongs to the Special Issue Vibrational Probes of Biomolecular Structure and Dynamics)

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16 pages, 4376 KiB

Open AccessArticle

Probing Coherent Vibrations of Organic Phosphonate Radical Cations with Femtosecond Time-Resolved Mass Spectrometry

by Derrick Ampadu Boateng, Mi’Kayla D. Word and Katharine Moore Tibbetts

Molecules 2019, 24(3), 509; https://doi.org/10.3390/molecules24030509 - 31 Jan 2019

Cited by 5 | Viewed by 3636

Abstract

Organic phosphates and phosphonates are present in a number of cellular components that can be damaged by exposure to ionizing radiation. This work reports femtosecond time-resolved mass spectrometry (FTRMS) studies of three organic phosphonate radical cations that model the DNA sugar-phosphate backbone: dimethyl methylphosphonate (DMMP), diethyl methylphosphonate (DEMP), and diisopropyl methylphosphonate (DIMP). Upon ionization, each molecular radical cation exhibits unique oscillatory dynamics in its ion yields resulting from coherent vibrational excitation. DMMP has particularly well-resolved 45 fs (

732 \pm 28

^{- 1}

) oscillations with a weak feature at 610–650 cm

^{- 1}

, while DIMP exhibits bimodal oscillations with a period of ∼55 fs and two frequency features at

554 \pm 28

and 670–720 cm

^{- 1}

. In contrast, the oscillations in DEMP decay too rapidly for effective resolution. The low- and high-frequency oscillations in DMMP and DIMP are assigned to coherent excitation of the symmetric O–P–O bend and P–C stretch, respectively. The observation of the same ionization-induced coherently excited vibrations in related molecules suggests a possible common excitation pathway in ionized organophosphorus compounds of biological relevance, while the distinct oscillatory dynamics in each molecule points to the potential use of FTRMS to distinguish among fragment ions produced by related molecules. Full article

(This article belongs to the Special Issue Vibrational Probes of Biomolecular Structure and Dynamics)

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12 pages, 2234 KiB

Open AccessArticle

pKa Determination of a Histidine Residue in a Short Peptide Using Raman Spectroscopy

by Brett H. Pogostin, Anders Malmendal, Casey H. Londergan and Karin S. Åkerfeldt

Molecules 2019, 24(3), 405; https://doi.org/10.3390/molecules24030405 - 23 Jan 2019

Cited by 23 | Viewed by 13176

Abstract

Determining the pKa of key functional groups is critical to understanding the pH-dependent behavior of biological proteins and peptide-based biomaterials. Traditionally, ¹H NMR spectroscopy has been used to determine the pKa of amino acids; however, for larger molecules and aggregating systems, this method can be practically impossible. Previous studies concluded that the C-D stretches in Raman are a useful alternative for determining the pKa of histidine residues. In this study, we report on the Raman application of the C2-D probe on histidine’s imidazole side chain to determining the pKa of histidine in a short peptide sequence. The pKa of the tripeptide was found via difference Raman spectroscopy to be 6.82, and this value was independently confirmed via ¹H NMR spectroscopy on the same peptide. The C2-D probe was also compared to other Raman reporters of the protonation state of histidine and was determined to be more sensitive and reliable than other protonation-dependent signals. The C2-D Raman probe expands the tool box available to chemists interested in directly interrogating the pKa’s of histidine-containing peptide and protein systems. Full article

(This article belongs to the Special Issue Vibrational Probes of Biomolecular Structure and Dynamics)

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14 pages, 2532 KiB

Open AccessArticle

Do Osmolytes Impact the Structure and Dynamics of Myoglobin?

by Dorota Kossowska, Kyungwon Kwak and Minhaeng Cho

Molecules 2018, 23(12), 3189; https://doi.org/10.3390/molecules23123189 - 03 Dec 2018

Cited by 8 | Viewed by 3862

Abstract

Osmolytes are small organic compounds that can affect the stability of proteins in living cells. The mechanism of osmolytes’ protective effects on protein structure and dynamics has not been fully explained, but in general, two possibilities have been suggested and examined: a direct interaction of osmolytes with proteins (water replacement hypothesis), and an indirect interaction (vitrification hypothesis). Here, to investigate these two possible mechanisms, we studied myoglobin-osmolyte systems using FTIR, UV-vis, CD, and femtosecond IR pump-probe spectroscopy. Interestingly, noticeable changes are observed in both the lifetime of the CO stretch of CO-bound myoglobin and the spectra of UV-vis, CD, and FTIR upon addition of the osmolytes. In addition, the temperature-dependent CD studies reveal that the protein’s thermal stability depends on molecular structure, hydrogen-bonding ability, and size of osmolytes. We anticipate that the present experimental results provide important clues about the complicated and intricate mechanism of osmolyte effects on protein structure and dynamics in a crowded cellular environment. Full article

(This article belongs to the Special Issue Vibrational Probes of Biomolecular Structure and Dynamics)

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9 pages, 1650 KiB

Open AccessArticle

Time-Resolved Spectroscopic Study of N,N-Di(4-bromo)nitrenium Ions in Selected Solutions

by Lili Du, Xin Lan, Zhiping Yan, Ruixue Zhu and David Lee Phillips

Molecules 2018, 23(12), 3182; https://doi.org/10.3390/molecules23123182 - 03 Dec 2018

Cited by 7 | Viewed by 2682

Abstract

Nitrenium ions are important reactive intermediates in chemistry and biology. In this work, femtosecond and nanosecond transient absorption (fs-TA and ns-TA) along with nanosecond time-resolved resonance Raman (ns-TR³) experiments were employed to examine the photochemical pathways of N-(4,4′-dibromodiphenylamino)-2,4,6-trimethylpyridinium BF₄⁻ (salt (DN) from just absorption of a photon of light to the production of the important N,N-di(4-bromophenyl)nitrenium ion 2. In acetonitrile (MeCN), the formation of halogenated diarylnitrenium ion 2 was observed within 4 ps, showing the vibrational spectra with strong intensity. The nucleophilic adduct reaction of ion 2 with H₂O was also examined in aqueous solutions. The direct detection of the unique ortho adduct intermediate 3 shows that there is an efficient and exclusive reaction pathway for 2 with H₂O. The results shown in this paper give new characterization of 2, which can be used to design time-resolved spectroscopy investigations of covalent addition reactions of nitrenium ions with other molecules in future studies. Full article

(This article belongs to the Special Issue Vibrational Probes of Biomolecular Structure and Dynamics)

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25 pages, 4139 KiB

Open AccessFeature PaperArticle

Excited State Structural Evolution of a GFP Single-Site Mutant Tracked by Tunable Femtosecond-Stimulated Raman Spectroscopy

by Longteng Tang, Liangdong Zhu, Miles A. Taylor, Yanli Wang, S. James Remington and Chong Fang

Molecules 2018, 23(9), 2226; https://doi.org/10.3390/molecules23092226 - 01 Sep 2018

Cited by 36 | Viewed by 4555

Abstract

Tracking vibrational motions during a photochemical or photophysical process has gained momentum, due to its sensitivity to the progression of reaction and change of environment. In this work, we implemented an advanced ultrafast vibrational technique, femtosecond-stimulated Raman spectroscopy (FSRS), to monitor the excited state structural evolution of an engineered green fluorescent protein (GFP) single-site mutant S205V. This mutation alters the original excited state proton transfer (ESPT) chain. By strategically tuning the Raman pump to different wavelengths (i.e., 801, 539, and 504 nm) to achieve pre-resonance with transient excited state electronic bands, the characteristic Raman modes of the excited protonated (A*) chromophore species and intermediate deprotonated (I*) species can be selectively monitored. The inhomogeneous distribution/population of A* species go through ESPT with a similar ~300 ps time constant, confirming that bridging a water molecule to protein residue T203 in the ESPT chain is the rate-limiting step. Some A* species undergo vibrational cooling through high-frequency motions on the ~190 ps time scale. At early times, a portion of the largely protonated A* species could also undergo vibrational cooling or return to the ground state with a ~80 ps time constant. On the photoproduct side, a ~1330 cm⁻¹ delocalized motion is observed, with dispersive line shapes in both the Stokes and anti-Stokes FSRS with a pre-resonance Raman pump, which indicates strong vibronic coupling, as the mode could facilitate the I* species to reach a relatively stable state (e.g., the main fluorescent state) after conversion from A*. Our findings disentangle the contributions of various vibrational motions active during the ESPT reaction, and offer new structural dynamics insights into the fluorescence mechanisms of engineered GFPs and other analogous autofluorescent proteins. Full article

(This article belongs to the Special Issue Vibrational Probes of Biomolecular Structure and Dynamics)

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Review

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21 pages, 1933 KiB

Open AccessReview

Vibrational Approach to the Dynamics and Structure of Protein Amyloids

by Haoqian Li, Richard Lantz and Deguo Du

Molecules 2019, 24(1), 186; https://doi.org/10.3390/molecules24010186 - 06 Jan 2019

Cited by 42 | Viewed by 5832

Abstract

Amyloid diseases, including neurodegenerative diseases such as Alzheimer’s and Parkinson’s, are linked to a poorly understood progression of protein misfolding and aggregation events that culminate in tissue-selective deposition and human pathology. Elucidation of the mechanistic details of protein aggregation and the structural features of the aggregates is critical for a comprehensive understanding of the mechanisms of protein oligomerization and fibrillization. Vibrational spectroscopies, such as Fourier transform infrared (FTIR) and Raman, are powerful tools that are sensitive to the secondary structure of proteins and have been widely used to investigate protein misfolding and aggregation. We address the application of the vibrational approaches in recent studies of conformational dynamics and structural characteristics of protein oligomers and amyloid fibrils. In particular, introduction of isotope labelled carbonyl into a peptide backbone, and incorporation of the extrinsic unnatural amino acids with vibrational moieties on the side chain, have greatly expanded the ability of vibrational spectroscopy to obtain site-specific structural and dynamic information. The applications of these methods in recent studies of protein aggregation are also reviewed. Full article

(This article belongs to the Special Issue Vibrational Probes of Biomolecular Structure and Dynamics)

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