Residue-Specific Conformational Heterogeneity of Proline-Rich Sequences Uncovered via Infrared Spectroscopy

Bukowski, Gregory S.; Thielges, Megan C.

doi:10.1021/acs.analchem.8b03813

Cited by 5 publications

(17 citation statements)

References 43 publications

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“…However, DFT calculations of vibrational frequencies have been reported for many C-D labeled amino acids, including glycine, alanine, proline, methionine, lysine, and histidine. 441,[444][445][446][447][448] For backbone Cα-D bonds and the γmethylene CD2 of proline, the calculated frequencies show dependence on amino acid conformation and therefore have been proposed as a way to measure local protein or peptide structure. Many experimental studies have taken advantage of the sensitivity to learn about protein or peptide conformational ensembles.…”

Section: C-d Stretch: Non-perturbative Ir Probementioning

confidence: 99%

“…Many experimental studies have taken advantage of the sensitivity to learn about protein or peptide conformational ensembles. 441,443,[448][449][450][451] An extensive QM/MM study reported by Corcelli and coworkers has aimed to account for the absorption lineshape of Cα-D backbone deuterated d1-alanine in aqueous solution; the power spectrum of the fluctuating electric dipole moment was determined from PM3 calculations of snapshots along a classical MD simulation. 452 In addition to investigating backbone structure, C-D probes have been introduced at side chains of amino acids to take advantage of their sensitivity to their local protein environment.…”

Section: C-d Stretch: Non-perturbative Ir Probementioning

confidence: 99%

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Vibrational Spectroscopic Map, Vibrational Spectroscopy, and Intermolecular Interaction

et al. 2020

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Vibrational spectroscopy is an essential tool in chemical analyses, biological assays, and studies of functional materials. Over the past decade, various coherent nonlinear vibrational spectroscopic techniques have been developed and enabled researchers to study time-correlations of the fluctuating frequencies that are directly related to solute-solvent dynamics, dynamical changes in molecular conformations and local electrostatic environments, chemical and biochemical reactions, protein structural dynamics and functions, characteristic processes of functional materials, and so on. In order to gain incisive and quantitative information on the local electrostatic environment, molecular conformation, protein structure and inter-protein contacts, ligand binding kinetics, and electric and optical properties of functional materials, a variety of vibrational probes have been developed and site-specifically incorporated into molecular, biological, and material systems for time-resolved vibrational spectroscopic investigation. However, still, an allencompassing theory that describes the vibrational solvatochromism, electrochromism, and dynamic fluctuation of vibrational frequencies has not been completely established mainly due to the intrinsic complexity of intermolecular interactions in condensed phases. In particular, the amount of data obtained from the linear and nonlinear vibrational spectroscopic experiments has been rapidly increasing, but the lack of a quantitative method to interpret these measurements has been one major obstacle in broadening the applications of these methods. Among various theoretical models, one of the most successful approaches is a semi-empirical model generally referred to as the vibrational spectroscopic map that is based on a rigorous theory of intermolecular interactions. Recently, genetic algorithm, neural network, and machine learning approaches have been applied to the development of vibrational solvatochromism theory. In this review, we provide comprehensive descriptions of the theoretical foundation and various examples showing its extraordinary successes in the interpretations of experimental observations. In addition, a brief introduction to a newly created repository website (http://frequencymap.org) for vibrational spectroscopic maps is presented. We anticipate that a combination of the vibrational frequency map approach and state-of-theart multidimensional vibrational spectroscopy will be one of the most fruitful ways to study the structure and dynamics of chemical, biological, and functional molecular systems in the future.

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Section: C-d Stretch: Non-perturbative Ir Probementioning

confidence: 99%

Section: C-d Stretch: Non-perturbative Ir Probementioning

confidence: 99%

Vibrational Spectroscopic Map, Vibrational Spectroscopy, and Intermolecular Interaction

et al. 2020

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“…Peptides with sequences Ac-VNKPLPPLPVA-NH 2 (pPbs2), Ac-VNKALPALPVA-NH 2 (p(P(−2,1)A)Pbs2), and Ac-APPIPPPRRKR-NH 2 (pNS5A) were synthesized by fluorenylmethoxycarbonyl solid-phase peptide synthesis as previously reported . N- and C-termini were acetylated and amidated, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…NMR spectroscopy is one of the most powerful approaches for gaining molecular-level information about flexible protein sequences, , but often the ensembles interconvert fast on the NMR timescale, so they remain difficult to fully capture. Other approaches, such as circular dichroism (CD) spectroscopy, small-angle X-ray scattering, and dynamic light scattering, provide only global views. − We have explored the use of site-specific infrared (IR) spectroscopy to characterize proline-rich (PR) sequences found in disordered regions of proteins and demonstrated the possibility to resolve rapidly interconverting states with residue-specific detail . Through expansion of the studies to several PR sequences and their recognition of two Src homology 3 (SH3) domains, we now provide evidence to support that these states play a role in the specificity and thermodynamics of molecular recognition.…”

Section: Introductionmentioning

confidence: 99%

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Involvement of Local, Rapid Conformational Dynamics in Binding of Flexible Recognition Motifs

2019

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Flexible protein sequences populate ensembles of rapidly interconverting states differentiated by small-scale fluctuations; however, elucidating whether and how the ensembles determine function experimentally is challenged by the combined high spatial and temporal resolution needed to capture the states. We used carbon–deuterium (C–D) bond vibrations incorporated as infrared probes to characterize with residue-specific detail the heterogeneity of states adopted by proline-rich (PR) sequences and assess their involvement in recognition of Src homology 3 domains. The C–D absorption envelopes provided evidence for two or three sub-populations at all proline residues. The changes in the subpopulations induced by binding generally reflected recognition by conformational selection but depended on the residue and the state of the ligand to illuminate distinct mechanisms among the PR ligands. Notably, the spectral data indicate that greater adaptability among the states is associated with reduced recognition specificity and that perturbation to the ensemble populations contributes to differences in binding entropy. Broadly, the study quantifies rapidly interconverting ensembles with residue-specific detail and implicates them in function.

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The shift of excitation spectra at blue edge of emission (BEEmS) as a new methodology to probe heterogeneity

Das,

Khan,

Sen

2024

Chemical Physics

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Residue-Specific Conformational Heterogeneity of Proline-Rich Sequences Uncovered via Infrared Spectroscopy

Cited by 5 publications

References 43 publications

Vibrational Spectroscopic Map, Vibrational Spectroscopy, and Intermolecular Interaction

Vibrational Spectroscopic Map, Vibrational Spectroscopy, and Intermolecular Interaction

Involvement of Local, Rapid Conformational Dynamics in Binding of Flexible Recognition Motifs

The shift of excitation spectra at blue edge of emission (BEEmS) as a new methodology to probe heterogeneity

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