Quarterly Reviews Of Biophysics[JOURNAL]
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200 papers
Computational methods for binding site prediction on macromolecules.
Kozlovskii I, Popov P
Q Rev Biophys · 2025 Mar · PMID 40071518 · Publisher ↗
Binding sites are key components of biomolecular structures, such as proteins and RNAs, serving as hubs for interactions with other molecules. Identification of the binding sites in macromolecules is essential for struct...
Binding sites are key components of biomolecular structures, such as proteins and RNAs, serving as hubs for interactions with other molecules. Identification of the binding sites in macromolecules is essential for structure-based molecular and drug design. However, experimental methods for binding site identification are resource-intensive and time-consuming. In contrast, computational methods enable large-scale binding site identification, structure flexibility analysis, as well as assessment of intermolecular interactions within the binding sites. In this review, we describe recent advances in binding site identification using machine learning methods; we classify the approaches based on the encoding of the macromolecule information about its sequence, structure, template knowledge, geometry, and energetic characteristics. Importantly, we categorize the methods based on the type of the interacting molecule, namely, small molecules, peptides, and ions. Finally, we describe perspectives, limitations, and challenges of the state-of-the-art methods with an emphasis on deep learning-based approaches. These computational approaches aim to advance drug discovery by expanding the druggable genome through the identification of novel binding sites in pharmacological targets and facilitating structure-based hit identification and lead optimization.
Protein Data Bank (PDB): Fifty-three years young and having a transformative impact on science and society.
Berman HM, Burley SK
Q Rev Biophys · 2025 Feb · PMID 39973356 · Publisher ↗
This review article describes the co-evolution of structural biology as a discipline and the Protein Data Bank (PDB), established in 1971 as the first open-access data resource in biology by like-minded structural scient...
This review article describes the co-evolution of structural biology as a discipline and the Protein Data Bank (PDB), established in 1971 as the first open-access data resource in biology by like-minded structural scientists. As the PDB archive grew in size and scope to encompass macromolecular crystallography, NMR spectroscopy, and cryo-electron microscopy, new technologies were developed to ingest, validate, curate, store, and distribute the information. Community engagement ensured that the needs of structural biologists (data depositors) and data consumers were met. Today, the archive houses more than 230,000 experimentally determined structures of proteins, nucleic acids, and macromolecular machines and their complexes with one another and small-molecule ligands. Aggregate costs of PDB data preservation are ~1% of the cost of structure determination. The enormous impact of PDB data on basic and applied research and education across the natural and medical sciences is presented and highlighted with illustrative examples. Enablement of protein structure prediction (AlphaFold2, RoseTTAfold, OpenFold, ) is the most widely appreciated benefit of having a corpus of rigorously validated, expertly curated 3D biostructure data.
Machinery, mechanism, and information in post-transcription control of gene expression, from the perspective of unstable RNA.
Paris G, Katsuya-Gaviria K, Luisi BF
Q Rev Biophys · 2025 Feb · PMID 39902476 · Publisher ↗
Throughout all the domains of life, and even among the co-existing viruses, RNA molecules play key roles in regulating the rates, duration, and intensity of the expression of genetic information. RNA acts at many differe...
Throughout all the domains of life, and even among the co-existing viruses, RNA molecules play key roles in regulating the rates, duration, and intensity of the expression of genetic information. RNA acts at many different levels in playing these roles. acting regulatory RNAs can modulate the lifetime and translational efficiency of transcripts with which they pair to achieve speedy and highly specific recognition using only a few components. -acting recognition elements, covalent modifications, and changes to the termini of RNA molecules encode signals that impact transcript lifetime, translation efficiency, and other functional aspects. RNA can provide an allosteric function to signal state changes through the binding of small ligands or interactions with other macromolecules. In either or , RNA can act in conjunction with multi-enzyme assemblies that function in RNA turnover, processing and surveillance for faulty transcripts. These enzymatic machineries have likely evolved independently in diverse life forms but nonetheless share analogous functional roles, implicating the biological importance of cooperative assemblies to meet the exact demands of RNA metabolism. Underpinning all the RNA-mediated processes are two key aspects: specificity, which avoids misrecognition, and speedy action, which confers timely responses to signals. How these processes work and how aberrant RNA species are recognised and responded to by the degradative machines are intriguing puzzles. We review the biophysical basis for these processes. Kinetics of assembly and multivalency of interacting components provide windows of opportunity for recognition and action that are required for the key regulatory events. The thermodynamic irreversibility of RNA-mediated regulation is one emergent feature of biological systems that may help to account for the apparent specificity and optimal rates.
Dynamics and kinetics in structural biology: the example of DNA photolyase.
Moffat K
Q Rev Biophys · 2025 Jan · PMID 39865994 · Publisher ↗
All biochemical reactions directly involve structural changes that may occur over a very wide range of timescales from femtoseconds to seconds. Understanding the mechanism of action thus requires determination of both th...
All biochemical reactions directly involve structural changes that may occur over a very wide range of timescales from femtoseconds to seconds. Understanding the mechanism of action thus requires determination of both the static structures of the macromolecule involved and short-lived intermediates between reactant and product. This requires either freeze-trapping of intermediates, for example by cryo-electron microscopy, or direct determination of structures in active systems at near-physiological temperature by time-resolved X-ray crystallography. Storage ring X-ray sources effectively cover the time range down to around 100 ps that reveal tertiary and quaternary structural changes in proteins. The briefer pulses emitted by hard X-ray free electron laser sources extend that range to femtoseconds, which covers critical chemical reactions such as electron transfer, isomerization, breaking of covalent bonds, and ultrafast structural changes in light-sensitive protein chromophores and their protein environment. These reactions are exemplified by the time-resolved X-ray studies by two groups of the FAD-based DNA repair enzyme, DNA photolyase, over the time range from 1 ps to 100 μs.
Allostery.
Montserrat-Canals M, Cordara G, Krengel U
Q Rev Biophys · 2025 Jan · PMID 39849666 · Publisher ↗
describes the ability of biological macromolecules to transmit signals spatially through the molecule from an site – a site that is distinct from binding sites of primary, endogenous ligands – to the functional or acti...
describes the ability of biological macromolecules to transmit signals spatially through the molecule from an site – a site that is distinct from binding sites of primary, endogenous ligands – to the functional or active site. This review starts with a historical overview and a description of the classical example of allostery – hemoglobin – and other well-known examples (aspartate transcarbamoylase, Lac repressor, kinases, G-protein-coupled receptors, adenosine triphosphate synthase, and chaperonin). We then discuss fringe examples of allostery, including intrinsically disordered proteins and inter-enzyme allostery, and the influence of dynamics, entropy, and conformational ensembles and landscapes on allosteric mechanisms, to capture the essence of the field. Thereafter, we give an overview over central methods for investigating molecular mechanisms, covering experimental techniques as well as simulations and artificial intelligence (AI)-based methods. We conclude with a review of allostery-based drug discovery, with its challenges and opportunities: with the recent advent of AI-based methods, allosteric compounds are set to revolutionize drug discovery and medical treatments.
S-layers: from a serendipitous discovery to a toolkit for nanobiotechnology.
Sleytr UB, Pum D
Q Rev Biophys · 2025 Jan · PMID 39819733 · Publisher ↗
Prokaryotic microorganisms, comprising and , exhibit a fascinating diversity of cell envelope structures reflecting their adaptations that contribute to their resilience and survival in diverse environments. Among these...
Prokaryotic microorganisms, comprising and , exhibit a fascinating diversity of cell envelope structures reflecting their adaptations that contribute to their resilience and survival in diverse environments. Among these adaptations, surface layers (S-layers) composed of monomolecular protein or glycoprotein lattices are one of the most observed envelope components. They are the most abundant cellular proteins and represent the simplest biological membranes that have developed during evolution. S-layers provide organisms with a great variety of selective advantages, including acting as an antifouling layer, protective coating, molecular sieve, ion trap, structure involved in cell and molecular adhesion, surface recognition and virulence factor for pathogens. In that possess S-layers as the exclusive cell wall component, the (glyco)protein lattices function as a cell shape-determining/maintaining scaffold. The wealth of information available on the structure, chemistry, genetics and and morphogenesis has revealed a broad application potential for S-layers as patterning elements in a molecular construction kit for bio- and nanotechnology, synthetic biology, biomimetics, biomedicine and diagnostics. In this review, we try to describe the scientifically exciting early days of S-layer research with a special focus on the 'Vienna-S-Layer-Group'. Our presentation is intended to illustrate how our curiosity and joy of discovery motivated us to explore this new structure and to make the scientific community aware of its relevance in the realm of prokaryotes, and moreover, how we developed concepts for exploiting this unique self-assembly structure. We hope that our presentation, with its many personal notes, is also of interest from the perspective of the history of S-layer research.
From resting potential to dynamics: advances in membrane voltage indicators and imaging techniques.
Shakibi R, Yazdipour F, Abadijoo H … +9 more , Manoochehri N, Rostami Pouria F, Bajooli T, Simaee H, Abdolmaleki P, Khatibi A, Abdolahad M, Moosavi-Movahhedi AA, Khayamian MA
Q Rev Biophys · 2025 Jan · PMID 39817368 · Publisher ↗
The membrane potential is a critical aspect of cellular physiology, essential for maintaining homeostasis, facilitating signal transduction, and driving various cellular processes. While the resting membrane potential (R...
The membrane potential is a critical aspect of cellular physiology, essential for maintaining homeostasis, facilitating signal transduction, and driving various cellular processes. While the resting membrane potential (RMP) represents a key physiological parameter, membrane potential fluctuations, such as depolarization and hyperpolarization, are equally vital in understanding dynamic cellular behavior. Traditional techniques, such as microelectrodes and patch-clamp methods, offer valuable insights but are invasive and less suited for high-throughput applications. Recent advances in voltage indicators, including fast and slow dyes, and novel imaging modalities such as second harmonic generation (SHG) and photoacoustic imaging, enable noninvasive, high-resolution measurement of both RMP and membrane potential dynamics. This review explores the mechanisms, development, and applications of these tools, emphasizing their transformative potential in neuroscience and cellular electrophysiology research.
Molecular mechanisms of the GABA type A receptor function.
Michałowski MA, Kłopotowski K, Wiera G … +2 more , Czyżewska MM, Mozrzymas JW
Q Rev Biophys · 2025 Jan · PMID 39806800 · Publisher ↗
The GABA type A receptor (GABAR) belongs to the family of pentameric ligand-gated ion channels and plays a key role in inhibition in adult mammalian brains. Dysfunction of this macromolecule may lead to epilepsy, anxiety...
The GABA type A receptor (GABAR) belongs to the family of pentameric ligand-gated ion channels and plays a key role in inhibition in adult mammalian brains. Dysfunction of this macromolecule may lead to epilepsy, anxiety disorders, autism, depression, and schizophrenia. GABAR is also a target for multiple physiologically and clinically relevant modulators, such as benzodiazepines (BDZs), general anesthetics, and neurosteroids. The first GABAR structure appeared in 2014, but the past years have brought a particularly abundant surge in structural data for these receptors with various ligands and modulators. Although the open conformation remains elusive, this novel information has pushed the structure-function studies to an unprecedented level. Electrophysiology, mutagenesis, photolabeling, and in silico simulations, guided by novel structural information, shed new light on the molecular mechanisms of receptor functioning. The main goal of this review is to present the current knowledge of GABAR functional and structural properties. The review begins with an outline of the functional and structural studies of GABAR, accompanied by some methodological considerations, especially biophysical methods, enabling the reader to follow how major breakthroughs in characterizing GABAR features have been achieved. The main section provides a comprehensive analysis of the functional significance of specific structural elements in GABARs. We additionally summarize the current knowledge on the binding sites for major GABAR modulators, referring to the molecular underpinnings of their action. The final chapter of the review moves beyond examining GABAR as an isolated macromolecule and describes the interactions of the receptor with other proteins in a broader context of inhibitory plasticity. In the final section, we propose a general conclusion that agonist binding to the orthosteric binding sites appears to rely on local interactions, whereas conformational transitions of bound macromolecule (gating) and allosteric modulation seem to reflect more global phenomena involving vast portions of the macromolecule.
Viroporins: discovery, methods of study, and mechanisms of host-membrane permeabilization.
Alcaraz A, Nieva JL
Q Rev Biophys · 2025 Jan · PMID 39806799 · Publisher ↗
The 'Viroporin' family comprises a number of mostly small-sized, integral membrane proteins encoded by animal and plant viruses. Despite their sequence and structural diversity, viroporins share a common functional trend...
The 'Viroporin' family comprises a number of mostly small-sized, integral membrane proteins encoded by animal and plant viruses. Despite their sequence and structural diversity, viroporins share a common functional trend: their capacity to assemble transmembrane channels during the replication cycle of the virus. Their selectivity spectrum ranges from low-pH-activated, unidirectional proton transporters, to size-limited permeating pores allowing passive diffusion of metabolites. Through mechanisms not fully understood, expression of viroporins facilitates virion assembly/release from infected cells, and subverts the cell physiology, contributing to cytopathogenicity. Compounds that interact with viroporins and interfere with their membrane-permeabilizing activity , are known to inhibit virus production. Moreover, viroporin-defective viruses comprise a source of live attenuated vaccines that prevent infection by notorious human and livestock pathogens. This review dives into the origin and evolution of the viroporin concept, summarizes some of the methodologies used to characterize the structure-function relationships of these important virulence factors, and attempts to classify them on biophysical grounds attending to their mechanisms of ion/solute transport across membranes.
Structural biology inside multicellular specimens using electron cryotomography.
Caspy I, Wang Z, Bharat TAM
Q Rev Biophys · 2025 Jan · PMID 39801355 · Full text
The electron cryomicroscopy (cryo-EM) resolution revolution has shifted structural biology into a new era, enabling the routine structure determination of macromolecular complexes at an unprecedented rate. Building on th...
The electron cryomicroscopy (cryo-EM) resolution revolution has shifted structural biology into a new era, enabling the routine structure determination of macromolecular complexes at an unprecedented rate. Building on this, electron cryotomography (cryo-ET) offers the potential to visualise the native three-dimensional organisation of biological specimens, from cells to tissues and even entire organisms. Despite this huge potential, the study of tissue-like multicellular specimens via cryo-ET still presents numerous challenges, wherein many steps in the workflow are being developed or in urgent need of improvement. In this review, we outline the latest techniques currently utilised for imaging of multicellular specimens, while clearly enumerating their associated limitations. We consider every step in typical workflows employed by various laboratories, including sample preparation, data collection and image analysis, to highlight recent progress and showcase prominent success stories. By considering the entire structural biology workflow for multicellular specimens, we identify which future exciting developments in hardware and software could enable comprehensive structural biology investigations, bringing forth a new age of discovery in molecular structural and cell biology.
Life and death of Yfh1: how cool is cold denaturation.
Temussi PA, Martin SR, Pastore A
Q Rev Biophys · 2025 Jan · PMID 39801016 · Publisher ↗
Yeast frataxin (Yfh1) is a small natural protein from yeast that has the unusual property of undergoing cold denaturation at temperatures above the freezing point of water when under conditions of low ionic strength. Thi...
Yeast frataxin (Yfh1) is a small natural protein from yeast that has the unusual property of undergoing cold denaturation at temperatures above the freezing point of water when under conditions of low ionic strength. This peculiarity, together with remarkable resilience, allows the determination, for the whole protein as well as for individual residues, of the stability curve, that is the temperature dependence of the free energy difference between the unfolded and folded forms. The ease of measuring stability curves without the need to add denaturants or introduce destabilizing mutations makes this protein an ideal 'tool' for investigating the influence of many environmental factors on protein stability. The present review aims at recapitulating all the open questions that Yfh1 has helped to address, including understanding the differences and commonalities of the cold, heat and pressure unfolded states. This protein thus offers a unique tool for studying aspects of protein stability so far been considered difficult to assess and provides important guidelines that could allow the identification of other similar systems.
Single-molecule orientation-localization microscopy: Applications and approaches.
Zhang O, Lew MD
Q Rev Biophys · 2024 Dec · PMID 39710866 · Full text
Single-molecule orientation-localization microscopy (SMOLM) builds upon super-resolved localization microscopy by imaging orientations and rotational dynamics of individual molecules in addition to their positions. This...
Single-molecule orientation-localization microscopy (SMOLM) builds upon super-resolved localization microscopy by imaging orientations and rotational dynamics of individual molecules in addition to their positions. This added dimensionality provides unparalleled insights into nanoscale biophysical and biochemical processes, including the organization of actin networks, movement of molecular motors, conformations of DNA strands, growth and remodeling of amyloid aggregates, and composition changes within lipid membranes. In this review, we discuss recent innovations in SMOLM and cover three key aspects: (1) biophysical insights enabled by labeling strategies that endow fluorescent probes to bind to targets with orientation specificity; (2) advanced imaging techniques that leverage the physics of light-matter interactions and estimation theory to encode orientation information with high fidelity into microscope images; and (3) computational methods that ensure accurate and precise data analysis and interpretation, even in the presence of severe shot noise. Additionally, we compare labeling approaches, imaging hardware, and publicly available analysis software to aid the community in choosing the best SMOLM implementation for their specific biophysical application. Finally, we highlight future directions for SMOLM, such as the development of probes with improved photostability and specificity, the design of “smart” adaptive hardware, and the use of advanced computational approaches to handle large, complex datasets. This review underscores the significant current and potential impact of SMOLM in deepening our understanding of molecular dynamics, paving the way for future breakthroughs in the fields of biophysics, biochemistry, and materials science.
Cryo-EM reconstruction of helical polymers: Beyond the simple cases.
Kreutzberger MAB, Sonani RR, Egelman EH
Q Rev Biophys · 2024 Dec · PMID 39658802 · Full text
Helices are one of the most frequently encountered symmetries in biological assemblies. Helical symmetry has been exploited in electron microscopic studies as a limited number of filament images, in principle, can provid...
Helices are one of the most frequently encountered symmetries in biological assemblies. Helical symmetry has been exploited in electron microscopic studies as a limited number of filament images, in principle, can provide all the information needed to do a three-dimensional reconstruction of a polymer. Over the past 25 years, three-dimensional reconstructions of helical polymers from cryo-EM images have shifted completely from Fourier-Bessel methods to single-particle approaches. The single-particle approaches have allowed people to surmount the problem that very few biological polymers are crystalline in order, and despite the flexibility and heterogeneity present in most of these polymers, reaching a resolution where accurate atomic models can be built has now become the standard. While determining the correct helical symmetry may be very simple for something like F-actin, for many other polymers, particularly those formed from small peptides, it can be much more challenging. This review discusses why symmetry determination can be problematic, and why trial-and-error methods are still the best approach. Studies of many macromolecular assemblies, such as icosahedral capsids, have usually found that not imposing symmetry leads to a great reduction in resolution while at the same time revealing possibly interesting asymmetric features. We show that for certain helical assemblies asymmetric reconstructions can sometimes lead to greatly improved resolution. Further, in the case of supercoiled flagellar filaments from bacteria and archaea, we show that the imposition of helical symmetry can not only be wrong, but is not necessary, and obscures the mechanisms whereby these filaments supercoil.
Graph theory approaches for molecular dynamics simulations.
Patel AC, Sinha S, Palermo G
Q Rev Biophys · 2024 Dec · PMID 39655478 · Full text
Graph theory, a branch of mathematics that focuses on the study of graphs (networks of nodes and edges), provides a robust framework for analysing the structural and functional properties of biomolecules. By leveraging m...
Graph theory, a branch of mathematics that focuses on the study of graphs (networks of nodes and edges), provides a robust framework for analysing the structural and functional properties of biomolecules. By leveraging molecular dynamics (MD) simulations, atoms or groups of atoms can be represented as nodes, while their dynamic interactions are depicted as edges. This network-based approach facilitates the characterization of properties such as connectivity, centrality, and modularity, which are essential for understanding the behaviour of molecular systems. This review details the application and development of graph theory-based models in studying biomolecular systems. We introduce key concepts in graph theory and demonstrate their practical applications, illustrating how innovative graph theory approaches can be employed to design biomolecular systems with enhanced functionality. Specifically, we explore the integration of graph theoretical methods with MD simulations to gain deeper insights into complex biological phenomena, such as allosteric regulation, conformational dynamics, and catalytic functions. Ultimately, graph theory has proven to be a powerful tool in the field of molecular dynamics, offering valuable insights into the structural properties, dynamics, and interactions of molecular systems. This review establishes a foundation for using graph theory in molecular design and engineering, highlighting its potential to transform the field and drive advancements in the understanding and manipulation of biomolecular systems.
Atomic molecular dynamics simulation advances of -designed proteins.
Wang M, Ma A, Wang H … +1 more , Lou X
Q Rev Biophys · 2024 Dec · PMID 39635823 · Publisher ↗
Proteins are vital biological macromolecules that execute biological functions and form the core of synthetic biological systems. The history of protein has evolved from initial successes in subordinate structural desig...
Proteins are vital biological macromolecules that execute biological functions and form the core of synthetic biological systems. The history of protein has evolved from initial successes in subordinate structural design to more intricate protein creation, challenging the complexities of natural proteins. Recent strides in protein design have leveraged computational methods to craft proteins for functions beyond their natural capabilities. Molecular dynamics (MD) simulations have emerged as a crucial tool for comprehending the structural and dynamic properties of -designed proteins. In this study, we examined the pivotal role of MD simulations in elucidating the sampling methods, force field, water models, stability, and dynamics of designed proteins, highlighting their potential applications in diverse fields. The synergy between computational modeling and experimental validation continued to play a crucial role in the creation of novel proteins tailored for specific functions and applications.
Review of contemporary fluorescence correlation spectroscopy method in diverse solution studies.
Jovičić SM
Q Rev Biophys · 2024 Oct · PMID 39465646 · Publisher ↗
Fluorescence correlation spectroscopy (FCS) is a well-known and established non-invasive method for quantification of physical parameters that preside over molecular mechanisms and dynamics. It combines maximum sensitivi...
Fluorescence correlation spectroscopy (FCS) is a well-known and established non-invasive method for quantification of physical parameters that preside over molecular mechanisms and dynamics. It combines maximum sensitivity and statistical confidence for the analysis of speed, size, and number of fluorescent molecules and interactions with surrounding molecules by time-averaging fluctuation analysis in a well-defined volume element. The narrow compass of this study is to acquaint the basic principle of diffusion and the FCS method in general regarding variable magnitudes and standardization adjustment. In this review, we give a theoretical introduction, examples of experimental applications, and utensils in solution systems with future perspectives.
Optical scattering methods for the label-free analysis of single biomolecules.
Gordon R, Peters M, Ying C
Q Rev Biophys · 2024 Oct · PMID 39443300 · Publisher ↗
Single-molecule techniques to analyze proteins and other biomolecules involving labels and tethers have allowed for new understanding of the underlying biophysics; however, the impact of perturbation from the labels and...
Single-molecule techniques to analyze proteins and other biomolecules involving labels and tethers have allowed for new understanding of the underlying biophysics; however, the impact of perturbation from the labels and tethers has recently been shown to be significant in several cases. New approaches are emerging to measure single proteins through light scattering without the need for labels and ideally without tethers. Here, the approaches of interference scattering, plasmonic scattering, microcavity sensing, nanoaperture optical tweezing, and variants are described and compared. The application of these approaches to sizing, oligomerization, interactions, conformational dynamics, diffusion, and vibrational mode analysis is described. With early commercial successes, these approaches are poised to have an impact in the field of single-molecule biophysics.
The development and applications of multidimensional biomolecular spectroscopy illustrated by photosynthetic light harvesting.
Fleming GR, Scholes GD
Q Rev Biophys · 2024 Oct · PMID 39434618 · Publisher ↗
The parallel and synergistic developments of atomic resolution structural information, new spectroscopic methods, their underpinning formalism, and the application of sophisticated theoretical methods have led to a step...
The parallel and synergistic developments of atomic resolution structural information, new spectroscopic methods, their underpinning formalism, and the application of sophisticated theoretical methods have led to a step function change in our understanding of photosynthetic light harvesting, the process by which photosynthetic organisms collect solar energy and supply it to their reaction centers to initiate the chemistry of photosynthesis. The new spectroscopic methods, in particular multidimensional spectroscopies, have enabled a transition from recording rates of processes to focusing on mechanism. We discuss two ultrafast spectroscopies - two-dimensional electronic spectroscopy and two-dimensional electronic-vibrational spectroscopy - and illustrate their development through the lens of photosynthetic light harvesting. Both spectroscopies provide enhanced spectral resolution and, in different ways, reveal pathways of energy flow and coherent oscillations which relate to the quantum mechanical mixing of, for example, electronic excitations (excitons) and nuclear motions. The new types of information present in these spectra provoked the application of sophisticated quantum dynamical theories to describe the temporal evolution of the spectra and provide new questions for experimental investigation. While multidimensional spectroscopies have applications in many other areas of science, we feel that the investigation of photosynthetic light harvesting has had the largest influence on the development of spectroscopic and theoretical methods for the study of quantum dynamics in biology, hence the focus of this review. We conclude with key questions for the next decade of this review.
Protonation constants of endo- and exogenous L-amino acids and their derivatives in aqueous and mixed solution: Unraveling molecular secrets.
Pająk M, Fichna J, Woźniczka M
Q Rev Biophys · 2024 Oct · PMID 39422089 · Publisher ↗
The aim of this review is to summarize the progress made in the determination of the protonation constants of biologically active ligands: endo- and exogenous L-amino acids and their derivatives in aqueous and mixed solu...
The aim of this review is to summarize the progress made in the determination of the protonation constants of biologically active ligands: endo- and exogenous L-amino acids and their derivatives in aqueous and mixed solutions using different experimental techniques. The knowledge of the protonation constants of the aforementioned ligands is crucial for the determination of the equilibrium constants of complex formation and thus for the understanding of complex biological reactions such as transamination, racemization, and decarboxylation. Thus, the protonation constants of ligands are a measure of their ability to form complexes with metal ions. This knowledge not only helps to understand fundamental biochemical processes, but also has practical applications in areas such as drug design, where ligands are often targeted for therapeutic purposes. The activity of the ligands tends to increase after complexation and their order is consistent with the values of the stepwise dissociation constants of the complexes formed. Understanding the properties of ligands by determining their protonation constants in different environments and their interactions with surrounding molecules is crucial to unraveling the complexity of biological systems.
Solution-based biophysical characterization of conformation change in structure-switching aptamers.
Eisen SR, Dauphin-Ducharme P, Johnson PE
Q Rev Biophys · 2024 Sep · PMID 39225237 · Publisher ↗
Structure-switching aptamers have become ubiquitous in several applications, notably in analytical devices such as biosensors, due to their ease of supporting strong signaling. Aside from their ability to bind specifical...
Structure-switching aptamers have become ubiquitous in several applications, notably in analytical devices such as biosensors, due to their ease of supporting strong signaling. Aside from their ability to bind specifically with their respective target, this class of aptamers also undergoes a conformational rearrangement upon target recognition. While several well-studied and early-developed aptamers (e.g., cocaine, ATP, and thrombin) have been found to have this structure-switching property, the vast majority do not. As a result, it is common to try to engineer aptamers into switches. This proves challenging in part because of the difficulty in obtaining structural and functional information about aptamers. In response, we review various readily available biophysical characterization tools that are capable of assessing structure switching of aptamers. In doing so, we delve into the fundamentals of these different techniques and detail how they have been utilized in characterizing structure-switching aptamers. While each of these biophysical techniques alone has utility, their real power to demonstrate the occurrence of structural change with ligand binding is when multiple techniques are used. We hope that through a deeper understanding of these techniques, researchers will be better able to acquire biophysical information about their aptamer-ligand systems and accelerate the translation of aptamers into biosensors.
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