Tsvi Tlusty

Ulsan National Institute of Science and Technology | UNIST · Institute for Basic Science.

The ribosome is a complex molecular machine that, in order to synthesize proteins, has to decode mRNAs by pairing their codons with matching tRNAs. Decoding is a major determinant of fitness and requires accurate and fast selection of correct tRNAs among many similar competitors. However, it is unclear whether the modern ribosome, and in particular...

Protein is matter of dual nature. As a physical object, a protein molecule is a folded chain of amino acids with diverse biochemistry. But it is also a point along an evolutionary trajectory determined by the function performed by the protein within a hierarchy of interwoven interaction networks of the cell, the organism, and the population. A phys...

The concept of quasiparticles—long-lived low-energy particle-like excitations—has become a cornerstone of condensed quantum matter, where it explains a variety of emergent many-body phenomena such as superfluidity and superconductivity. Here we use quasiparticles to explain the collective behaviour of a classical system of hydrodynamically interact...

In everyday life, rolling motion is typically associated with cylindrical (for example, car wheels) or spherical (for example, billiard balls) bodies tracing linear paths. However, mathematicians have, for decades, been interested in more exotically shaped solids such as the famous oloids¹, sphericons², polycons³, platonicons⁴ and two-circle roller...

AlphaFold2 (AF2) is a promising tool for structural biology, but is it sufficiently accurate to predict the effect of missense mutations? We find that structural variation between closely related 1-3 mutations) protein pairs is correlated across experimental and AF2-predicted structures (${\sim}90000$ pairs). Analysis of ${\sim}10000$ predicted str...

AI algorithms have proven to be excellent predictors of protein structure, but whether and how much these algorithms can capture the underlying physics remains an open question. Here, we aim to test this question using the Alphafold2 (AF) algorithm: We use AF to predict the subtle structural deformation induced by single mutations, quantified by st...

Tissues in multicellular organisms are immensely diverse: animal tissues include sheet-like epithelia, bundles of syncitial muscle fibres and the branched and interconnected nerves, while plants contain sheet-like epidermis and highly organized bundles of vascular tissue. However, at the microanatomical level, tissues are notably similar in that th...

The number of possible melodies is unfathomably large, yet despite this virtually unlimited potential for melodic variation, melodies from different societies can be surprisingly similar. The motor constraint hypothesis accounts for certain similarities, such as scalar motion and contour shape, but not for other major common features, such as repet...

The standard theory of musical scales since antiquity has been based on harmony, rather than melody. Some recent analyses support either view, and we lack a comparative test on cross-cultural data. We address this longstanding problem through a rigorous, computational comparison of the main theories against 1,314 scales from 96 countries. There is...

Despite recent breakthroughs in understanding how protein sequence relates to structure and function, considerably less attention has been paid to the general features of protein surfaces beyond those regions involved in binding and catalysis. This article provides a systematic survey of the universe of protein surfaces and quantifies the sizes, sh...

Despite recent breakthroughs in understanding how protein sequence relates to structure and function, considerably less attention has been paid to the general features of protein surfaces beyond those regions involved in binding and catalysis. This paper provides a systematic survey of the universe of protein surfaces and quantifies the sizes, shap...

A cylinder will roll down an inclined plane in a straight line. A cone will roll around a circle on that plane and then will stop rolling. We ask the inverse question: For which curves drawn on the inclined plane $\mathbb{R}^2$ can one carve a shape that will roll downhill following precisely this prescribed curve and its translationally repeated c...

Proteins are intricate molecular machines whose complexity arises from the heterogeneity of the amino acid building blocks and their dynamic network of many-body interactions. These nanomachines gain function when put in the context of a whole organism through interaction with other inhabitants of the biological realm. And this functionality shapes...

Crystallization on spherical surfaces is obliged by topology to induce lattice defects. But controlling the organization of such defects remains a great challenge due to the long-range constraints of the curved geometry. Here, we report on DNA-coated colloids whose programmable interaction potentials can be used to regulate the arrangement of defec...

Scales, sets of discrete pitches that form the basis of melodies, are thought to be one of the most universal hallmarks of music. But we know relatively little about cross-cultural diversity of scales or how they evolved. To remedy this, we assemble a cross-cultural database (Database of Musical Scales: DaMuSc) of scale data, collected over the pas...

AlphaFold2 (AF) is a promising tool, but is it accurate enough to predict single mutation effects? Here, we report that the localized structural deformation between protein pairs differing by only 1–3 mutations—as measured by the effective strain—is correlated across 3901 experimental and AF-predicted structures. Furthermore, analysis of ∼11 000 pr...

Proteins are intricate molecular machines whose complexity arises from the heterogeneity of the amino acid building blocks and their dynamic network of many-body interactions. These nanomachines gain function when put in the context of a whole organism through interaction with other inhabitants of the biological realm. And this functionality shapes...

Background Over evolutionary timescales, genomic loci can switch between functional and non-functional states through processes such as pseudogenization and de novo gene birth. Particularly, de novo gene birth is a widespread process, and many examples continue to be discovered across diverse evolutionary lineages. However, the general mechanisms t...

AlphaFold2 (AF) is an excellent structure predictor, but it does not unambiguously indicate whether the predicted structure is stable. Could it be that AF contains sufficient information to predict protein stability, and one just needs a way to extract it? To address this question, we investigate single-mutation effects on protein stability using a...

We introduce an RG-inspired coarse-graining for extracting the collective features of data. The key to successful coarse-graining lies in finding appropriate pairs of data sets. We coarse-grain the two closest data in a regular real-space RG in a lattice while considers the overall information loss in momentum-space RG. Here we compromise the two m...

We report on the experimental observation of stochastic resonance (SR) in a nonGaussian active bath without any periodic modulation. A Brownian particle hopping in a nanoscale double-well potential under the influence of nonGaussian correlated noise, with mean interval τP and correlation time τc, shows a series of equally-spaced peaks in the reside...

Nanoswimmers are ubiquitous in biotechnology and nanotechnology but are extremely challenging to measure due to their minute size and driving forces. A simple method is proposed for detecting the elusive physical features of nanoswimmers by observing how they affect the motion of much larger, easily traceable particles. Modeling the swimmers as hyd...

Nanoswimmers are ubiquitous in bio- and nano-technology but are extremely challenging to measure due to their minute size and driving forces. A simple method is proposed for detecting the elusive physical features of nanoswimmers by observing how they affect the motion of much larger, easily traceable particles. Modeling the swimmers as hydrodynami...

Proteins need to selectively interact with specific targets among a multitude of similar molecules in the cell. But despite a firm physical understanding of binding interactions, we lack a general theory of how proteins evolve high specificity. Here, we present such a model that combines chemistry, mechanics and genetics, and explains how their int...

A bstract Over evolutionary timescales, genomic loci switch between functional and non-functional states through processes such as pseudogenization and de novo gene birth. Here we ask about the likelihood and rate of functionalization of non-functional loci. We simulate an evolutionary model to look at the contributions of mutations and structural...

Variation of positional information, measured by the two-body excess entropy $\S{2}$, is studied across the liquid-solid equilibrium transition in a simple two-dimensional system. Analysis reveals a master relation between $\S{2}$ and the freezing temperature $\Tf$, from which a scaling law is extracted: $-\S{2}\sim (T-\Tf)^{-1/3}$. Theoretical and...

Living systems have evolved to efficiently consume available energy sources using an elaborate circuitry of chemical reactions which, puzzlingly, bear a strict restriction to asymmetric chiral configurations. While autocatalysis is known to promote such chiral symmetry breaking, whether a similar phenomenon may also be induced in a more general cla...

The cellular milieu is teeming with biochemical nano-machines whose activity is a strong source of correlated non-thermal fluctuations termed active noise. Essential elements of this circuitry are enzymes, catalysts that speed up the rate of metabolic reactions by orders of magnitude, thereby making life possible. Here, we examine the possibility t...

The concept of quasiparticles -- long-lived low-energy particle-like excitations -- has become a keystone of condensed quantum matter, where it explains a variety of emergent many-body phenomena, such as superfluidity and superconductivity. Here, we use quasiparticles to explain the collective behavior of a classical system of hydrodynamically inte...

Proteins need to selectively interact with specific targets among a multitude of similar molecules in the cell. But despite a firm physical understanding of binding interactions, we lack a general theory of how proteins evolve high specificity. Here, we present such a model that combines chemistry, mechanics and genetics, and explains how their int...

Proteins are translated from the N to the C terminus, raising the basic question of how this innate directionality affects their evolution. To explore this question, we analyze 16,200 structures from the Protein Data Bank (PDB). We find remarkable enrichment of α helices at the C terminus and β strands at the N terminus. Furthermore, this α-β asymm...

Rapid advance of experimental techniques provides an unprecedented in-depth view into complex developmental processes. Still, little is known on how the complexity of multicellular organisms evolved by elaborating developmental programs and inventing new cell types. A hurdle to understanding developmental evolution is the difficulty of even describ...

Contrary to long-held views, recent evidence indicates that de novo birth of genes is not only possible but is surprisingly prevalent: a substantial fraction of eukaryotic genomes are composed of orphan genes, which show no homology with any conserved genes. And a remarkably large proportion of orphan genes likely originated denovo from non-genic r...

Living systems have evolved to efficiently consume available energy sources using an elaborate circuitry of chemical reactions, which are puzzlingly restricted to specific chiral configurations. While autocatalysis is known to induce such chiral symmetry breaking, whether this might also arise in a more general class of non-autocatalytic chemical n...

Scales, sets of discrete pitches that form the basis of melodies, are thought to be one of the most universal hallmarks of music. But we know relatively little about cross-cultural diversity of scales or how they evolved. To remedy this, we assemble a cross-cultural database (Database of Musical Scales: DaMuSc) of scale data, collected over the pas...

Rapid advance of experimental techniques provides an unprecedented in-depth view into complex developmental processes. Still, little is known on how the complexity of multicellular organisms evolved by elaborating developmental programs and inventing new cell types. A hurdle to understanding developmental evolution is the difficulty of even describ...

Hydrodynamics is shown to induce non-Hermitian topological phenomena in ordinary, passive soft matter. This is demonstrated by subjecting a two-dimensional elastic lattice to a low-Reynolds viscous flow. The interplay of hydrodynamics and elasticity splits Dirac cones into bulk Fermi arcs, pairing exceptional points with opposite half-integer topol...

The unprecedented prowess of measurement techniques provides a detailed, multi‐scale look into the depths of living systems. Understanding these avalanches of high‐dimensional data—by distilling underlying principles and mechanisms—necessitates dimensional reduction. We propose that living systems achieve exquisite dimensional reduction, originatin...

We report on the observation of bona fide stochastic resonance (SR) in a nonGaussian active bath without any periodic forcing. Particles hopping in a nanoscale double-well potential under the influence of correlated Poisson noise display a series of equally-spaced peaks in the residence time distribution. Maximal peaks are measured when the mean re...

We report on the observation of bona fide stochastic resonance (SR) in a nonGaussian active bath without any periodic forcing. Particles hopping in a nanoscale double-well potential under the influence of correlated Poisson noise display a series of equally-spaced peaks in the residence time distribution. Maximal peaks are measured when the mean re...

Variation of positional information, measured by the two-body excess entropy $\mathsf{S}_\mathrm{2}$, is studied across the liquid-solid equilibrium transition in a simple two-dimensional system. Analysis reveals a master relation between $\mathsf{S}_\mathrm{2}$ and the freezing temperature $T_{\mathrm{f}}$, from which a scaling law is extracted: $...

Background Multicellular organisms are characterized by a wide diversity of forms and complexity despite a restricted set of key molecules and mechanisms at the base of organismal development. Development combines three basic processes—asymmetric cell division, signaling, and gene regulation—in a multitude of ways to create this overwhelming divers...

The cellular milieu is teeming with biochemical nano-machines whose activity is a strong source of correlated non-thermal fluctuations termed ''active noise''. Essential elements of this circuitry are enzymes, catalysts that speed up the rate of metabolic reactions by orders of magnitude, thereby making life possible. Here, we examine the possibili...

The unprecedented prowess of measurement techniques provides a detailed, multi-scale look into the depths of living systems. But understanding these avalanches of high-dimensional data -- by distilling underlying principles of more general nature -- necessitates dimensional reduction. We will explain how some geometric insights by mathematicians al...

Open non-Hermitian systems exhibit unique topological hallmarks that are absent from their isolated Hermitian counterparts. Our model system demonstrates that these exotic topological phenomena can be induced in the spectra of generic elastic lattices simply by subjecting them to viscous flow. The interplay of hydrodynamics and elasticity splits Di...

The design of small scale nonequilibrium steady states (NESS) is a challenging, open ended question. While similar equilibrium problems are tractable using standard thermodynamics, a generalized description for nonequilibrium systems is lacking, making the design problem particularly difficult. Here we show we can exploit the large-deviation behavi...

Günther et al . report that their control experiment using randomized magnetic field gradient sequences disagreed with findings we had reported using linear gradients. However, we show that measurements in our laboratory are consistent using both methods.

h2>Günther et al. report that their control experiment using randomized magnetic field gradient sequences disagreed with findings we had reported using linear gradients. However, we show that measurements in our laboratory are consistent using both methods. </h2

Significance The literature is inconsistent regarding evidence for boosted molecular mobility during enzyme catalysis, a phenomenon that challenges the common tenet that enzyme mobility is governed solely by Brownian motion. This paper surveys 10 different catalytic enzymes and shows that magnitude of enhanced diffusion scales with energy release r...

Whirling and swerving, a bacterium is swimming in a test tube, foraging for food. On the surface of a vibrating bath, a droplet starts walking. A certain similarity, but mostly dissimilarity, between the physical memory that emerges in Couder's droplet experiments and the biological memory of the bacterium is noted. It serves as a starting point fo...

Whirling and swerving, a bacterium is swimming in a test tube, foraging for food. On the surface of a vibrating bath, a droplet starts walking. A certain similarity, but mostly dissimilarity, between the physical memory that emerges in Couder’s droplet experiments and the biological memory of the bacterium is noted. It serves as a starting point fo...

The design of small scale non-equilibrium steady states (NESS) is a challenging, open ended question. While similar equilibrium problems are tractable using standard thermodynamics, a generalized description for non-equilibrium systems is lacking, making the design problem particularly difficult. Here we show we can exploit the large deviation beha...

Molecular agitation more rapid than thermal Brownian motion is reported for cellular environments, motor proteins, synthetic molecular motors, enzymes, and common chemical reactions, yet that chemical activity couples to molecular motion contrasts with generations of accumulated knowledge about diffusion at equilibrium. To test the limits of this i...

Proteins are translated from the N- to the C-terminal, raising the basic question of how this innate directionality affects their evolution. To explore this question, we analyze 16,200 structures from the protein data bank (PDB). We find remarkable enrichment of $\alpha$-helices at the C terminal and $\beta$-sheets at the N terminal. Furthermore, t...

Thermodynamic uncertainty relations (TURs) set fundamental bounds on the fluctuation and dissipation of stochastic systems. Here, we examine these bounds, in experiment and theory, by exploring the entire phase space of a cyclic information engine operating in a non-equilibrium steady state. Close to its maximal efficiency, we find that the engine...

Chaperone proteins --- the most disordered among all protein groups --- help RNAs fold into their functional structure by destabilizing misfolded configurations or stabilizing the functional ones. But disentangling the mechanism underlying RNA chaperoning is challenging, mostly due to inherent disorder of the chaperones and the transient nature of...

Reactions give solvents a kick During a chemical reaction, the reorganization of solvent molecules not directly in contact with reactants and products is normally viewed as a simple diffusion response. Wang et al. studied molecular diffusion in six common reactions—including the copper-catalyzed click reaction and the Diels-Alder reaction—with puls...

To mitigate errors induced by the cell's heterogeneous noisy environment, its main information channels and production networks utilize the kinetic proofreading (KPR) mechanism. Here, we examine two extensively studied KPR circuits, DNA replication by the T7 DNA polymerase and translation by the E. coli ribosome. Using experimental data, we analyze...

Understanding noisy information engines is a fundamental problem of non-equilibrium physics, particularly in biomolecular systems agitated by thermal and active fluctuations in the cell. By the generalized second law of thermodynamics, the efficiency of these engines is bounded by the mutual information passing through their noisy feedback loop. Ye...

The Supercritical Fluid (SCF) is known to exhibit salient dynamic and thermodynamic crossovers and inhomogeneous molecular distribution. But the question as to what basic physics underlies these microscopic and macroscopic anomalies remains open. Here, using an order parameter extracted by machine learning, the fraction of gas-like (or liquid-like)...

The concept that catalytic enzymes can act as molecular machines transducing chemical activity into motion has concep-tual and experimental support, but experimental support has involved oligomeric enzymes, often studied under conditions where the substrate concentration is higher than biologically relevant and accordingly exceeds kM, the Michaelis...

For efficient performance, stochastic engines, in particular information engines, need to minimize simultaneously the energy dissipation and the fluctuations in the extracted work. However, recently discovered thermodynamic uncertainty bounds constrain this optimization by setting tradeoff relations between dissipation and fluctuation. Whether thes...

Understanding noisy information engines is a fundamental problem of non-equilibrium physics, particularly in biomolecular systems agitated by thermal and active fluctuations in the cell. By the generalized second law of thermodynamics, the efficiency of these engines is bounded by the mutual information passing through their noisy feedback loop. Ye...

To transform a single-celled zygote into an adult multicellular organism, development employs three basic processes--asymmetric cell division, signaling and gene regulation. These three processes can be combined in a multitude of ways, thus generating the huge diversity of plant and animal forms we see today. The wealth of possible developmental sc...

To mitigate errors induced by the cell's heterogeneous noisy environment, its main information channels and production networks utilize the kinetic proofreading (KPR) mechanism. Here, we examine two extensively-studied KPR circuits, DNA replication by the T7 DNA polymerase and translation by the E. coli ribosome. Using experimental data, we analyze...

Chaperone proteins - the most disordered among all protein groups - help RNAs fold into their functional structure by destabilizing misfolded configurations or stabilizing the functional ones. But disentangling the mechanism underlying RNA chaperoning is challenging, mostly due to inherent disorder of the chaperones and the transient nature of thei...

We demonstrate that the oft-reported enhanced diffusion of certain enzymes at substrate concentrations above biological concentrations, meaning above kM (the Michaelis-Menten constant), can be accounted for by dissociation of these oligomeric enzymes into their smaller subunits. Our measurements based on using four independent techniques, static li...

Proteins are a matter of dual nature. As a physical object, a protein molecule is a folded chain of amino acids with multifarious biochemistry. But it is also an instantiation along an evolutionary trajectory determined by the function performed by the protein within a hierarchy of interwoven interaction networks of the cell, the organism and the p...

Musical scales are used in cultures throughout the world, but the question as to how they evolved remains open. Some suggest that scales based on the harmonic series are inherently pleasant, while others propose that scales are chosen that are easy to sing, hear and reproduce accurately. However, testing these theories has been hindered by the spar...

The Supercritical Fluid (SCF) is known to exhibit salient dynamic and thermodynamic crossovers and inhomogeneous molecular distribution. But the question as to what basic physics underlies these microscopic and macroscopic anomalies remains open. Here, using an order parameter extracted by machine learning, the fraction of gas-like (or liquid-like)...

Significance Catalysis and mobility of reactants in fluid are normally thought to be decoupled. Violating this classical paradigm, this paper presents the catalyst laws of motion. Comparing experimental data to the theory presented here, we conclude that part of the free energy released by chemical reaction is channeled into driving catalysts to ex...