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We examine the interplay of motility and information exchange in a model of run-and-tumble active particles where the particle's motility is encoded as a bit of information that can be exchanged upon contact according to the rules of AND and OR logic gates in a circuit. Motile AND particles become non-motile upon contact with a non-motile particle. Conversely, motile OR particles remain motile upon collision with their non-motile counterparts. AND particles that have become non-motile additionally "reawaken", i.e., recover their motility, at a fixed rate $\mu$, as in the SIS (Susceptible, Infected, Susceptible) model of epidemic spreading, where an infected agent can become healthy again, but keeps no memory of the recent infection, hence it is susceptible to a renewed infection. For $\mu=0$, both AND and OR particles relax irreversibly to absorbing states of all non-motile or all motile particles, respectively. The relaxation kinetics is, however, faster for OR particles that remain active throughout the process. At finite $\mu$, the AND dynamics is controlled by the interplay between reawakening and collision rates. The system evolves to a state of all motile particles (an absorbing state in the language of absorbing phase transitions) for $\mu>\mu_c$ and to a mixed state with coexisting motile and non-motile particles (an active state in the language of absorbing phase transitions) for $\mu

Fluorine-containing 1,3-dicarbonyl derivatives are essential building blocks for drug discovery and manufacture. To understand the factors that determine selectivity between mono- and di-fluorination of 1,3-dicarbonyls systems, we have performed kinetic studies of keto-enol tautomerism and fluorination processes. Photoketonization of 1,3-diaryl-1,3-dicarbonyl derivatives and their 2-fluoro analogues is coupled with relaxation kinetics to determine enolization rates. Reaction additives such as water accelerate enolization processes, especially of 2-fluoro-1,3-dicarbonyl systems. Kinetic studies of enol fluorination with Selectfluor™ and NFSI reveal the quantitative effects of 2-fluorination upon enol nucleophilicity towards reagents of markedly different electrophilicity. Our findings have important implications for the synthesis of α,α-difluoroketonic compounds, providing valuable quantitative information to aid in the design of fluorination and difluorination reactions.

17 p.-7 fig., Polyhydroxyalkanoates (PHA) are polyesters produced intracellularly by many bacterial species as energy storage materials, which are used in biomedical applications, including drug delivery systems, due to their biocompatibility and biodegradability. In this study, we evaluated the potential application of this nanomaterial as a basis of inhaled drug delivery systems. To that end, we assessed the possible interaction between PHA nanoparticles (NPs) and pulmonary surfactant using dynamic light scattering, Langmuir balances, and epifluorescence microscopy. Our results demonstrate that NPs deposited onto preformed monolayers of DPPC or DPPC/POPG bind these surfactant lipids. This interaction facilitated the translocation of the nanomaterial towards the aqueous subphase, with the subsequent loss of lipid from the interface. NPs that remained at the interface associated with liquid expanded (LE)/tilted condensed (TC) phase boundaries, decreasing the size of condensed domains and promoting the intermixing of TC and LE phases at submicroscopic scale. This provided the stability necessary for attaining high surface pressures upon compression, countering the destabilization induced by lipid loss. These effects were observed only for high NP loads, suggesting a limit for the use of these NPs in pulmonary drug delivery., Research in the laboratory of the authors is currently funded by grants from the Spanish Ministry of Science, Universities and Innovation (RTI2018-094564-B-I00, BIO2017-83448-R) and the Regional Government of Madrid (P2018/NMT-4389).

Treballs Finals de Grau de Física, Facultat de Física, Universitat de Barcelona, Curs: 2021, Tutors: Marta Gironella-Torrent, Fèlix Ritort, We use a soft-glass mechanical (SGM) model to reproduce the experimental force relaxation curves of red blood cells (RBC) measured by laser optical tweezers (LOT). The relaxation experiments consist in applying a deformation step jump and observe how the force, after reaching a maximum, decreases with time. The SGM model has been already successful to reproduce the LOT experimental pulling cycles of erythrocytes. We extend our model to reproduce the experimental relaxation curves if nicely predicts the stationary force of the relaxation in terms of the maximum force achieved immediately after the extension step-jump

The kinetics and mechanism of the cis dihydroxylation of cis‐1, 2‐ dichloroethylene, trans‐1, 2‐dichloroethylene, and trichloroethylene by osmium tetroxide was studied systematically in aqueous solution. The stoichiometry of the process was determined based on the principle of continuous variation of reactant ratios with spectrophotometric detection. The results always showed 1:1 stoichiometry, which is in agreement with dihydroxylation. All three reactions were found to proceed in two distinct steps. The first step occurred on a time scale of seconds and was associated with a minor change in absorbance and was identified as the formation of a 1:1 adduct between the two reagents, which is the osmium(VI) ester that plays a decisive role in catalytic applications. This species is formed in an equilibrium that is very much shifted toward the reactants, so the osmium(VI) complex is a short‐lived intermediate of the process, which is detected kinetically, but its concentration is never high enough for structural characterization. The second reaction is accompanied by major spectral changes ; it involves the formation of the final products. Our results clearly show that it is possible to detect the intermediate of the process by careful kinetic studies. It is also possible that the same strategy might be successful in other OsO4‐dependent dihydroxylation processes.

A series of rubrene derivatives were synthesized and the influence of the side group in enhancing photo-oxidative stability was evaluated. Photo-oxidation half-lives were determined via UV-vis absorption spectroscopy, which revealed thiophene containing derivatives to be the most stable species. The electron affinity of the compounds did not correlate with stability as previously reported in literature. Our work shows that shorter excited-state lifetimes result in increased photo-oxidative stability in these rubrene derivatives. These results confirm that faster relaxation kinetics out-compete the formation of reactive oxygen species that ultimately degrade linear oligoacenes. This report highlights the importance of using molecular design to tune excited-state lifetimes in order to generate more stable oligoacenes.

Thermally evaporated chalcogenide glass thin films are known to be highly photosensitive revealing both metastable and transient photoinduced changes of optical transmission at the fundamental absorption edge region. In-situ kinetics of metastable photobleaching and transient photodarkening as well as following light-off relaxations for as-deposited GeSe2 thin films were studied and fitted with the stretched exponential function. Dependences of kinetic parameters beta and tau a on film thickness, temperature, sample prehistory and wavelength of light irradiation were analyzed. The obtained results were discussed within current approaches to mechanisms of photoinduced kinetic phenomena and structural relaxation in glasses. Vakuově napařené tenké vrstvy chalkogenidových skel jsou známé pro svoji vysokou fotocitlivost odhalující metastabilní a přechodné fotoindukované změny optické propustnosti v regionu fundamentální absorpční hrany. Byly studovány a fitovány n-situ kinetiky metastabilního fotosvětlání a přechodného fototmavnutí čerstvě deponovaných vrstev GeSe2, jakožto i relaxace při vypnutí zdroje expozice. Byla analyzována závislost parametrů kinetiky beta a tau na tloušťce, teplotě, historii vzorku a vlnové délce použitého záření. Získané výsledky byly diskutovány v rámci současných přístupů k mechanismům fotoindukovaných jevů a strukturální relaxace ve sklech.

cTnI(P82S) (cTnI(P83S) in rodents) resides at the I-T arm of cardiac troponin I (cTnI) and was initially identified as a disease-causing mutation of hypertrophic cardiomyopathy (HCM). However, later studies suggested this may not be true. We recently reported that introduction of an HCM-associated mutation in either inhibitory-peptide (cTnI(R146G)) or cardiac-specific N-terminus (cTnI(R21C)) of cTnI blunts the PKA-mediated modulation on myofibril activation/relaxation kinetics by prohibiting formation of intrasubunit contacts between these regions. Here, we tested whether this also occurs for cTnI(P83S). cTnI(P83S) increased both Ca(2+) binding affinity to cTn (KCa) and affinity of cTnC for cTnI (KC-I), and eliminated the reduction of KCa and KC-I observed for phosphorylated-cTnI(WT). In isolated myofibrils, cTnI(P83S) maintained maximal tension (TMAX) and Ca(2+) sensitivity of tension (pCa50). For cTnI(WT) myofibrils, PKA-mediated phosphorylation decreased pCa50 and sped up the slow-phase relaxation (especially for those Ca(2+) conditions that heart performs in vivo). Those effects were blunted for cTnI(P83S) myofibrils. Molecular-dynamics simulations suggested cTnI(P83S) moderately inhibited an intrasubunit interaction formation between inhibitory-peptide and N-terminus, but this "blunting" effect was weaker than that with cTnI(R146G) or cTnI(R21C). In summary, cTnI(P83S) has similar effects as other HCM-associated cTnI mutations on troponin and myofibril function even though it is in the I-T arm of cTnI.

The slow non-monotonic relaxation processes, which have been recently fixed in Al-Y melts, are described theoretically. The theoretical description is based on the Cahn-Hilliard theory and functional methods of non-equilibrium dynamics. In terms of the suggested approach the reasons of this relaxation kinetics are non-linearity of the system near to the liquidus line, which sharply increases with Y concentration, and strong initial heterogeneity of the melt on the concentration of Y atoms. According to our analysis one can conclude that the non-monotonic temporal dependence of viscosity is caused by the Ostwald ripening processes in the rich in yttrium areas., Comment: Submitted in Physica A

Вивчено кiнетику встановлення рiвноваги водних розчинiв спиртiв. Запропоновано мо-дель нерiвноважного стану водно-спиртового розчину, згiдно з якою повiльну релакса-цiю розчину пов’язано з руйнуванням зародкiв нової фази. Процес руйнування описаноза допомогою лагранжевого формалiзму i теорiї нуклеацiї. Зроблено розрахунки коефiцi-єнта самодифузiї молекул з поверхнi зародку за допомогою якого проведено оцiнку часуруйнування зародкiв i часу їх життя в залежностi вiд розмiру. Встановлено зв’язокмiж коефiцiєнтом дифузiї у просторi зародкiв i коефiцiєнтом молекулярної самодифузiїз поверхнi зародкiв. Проведено порiвняння з наявними експериментальними даними., The kinetics of relaxation processes in aqueous alcoholic solutions has been studied. A modelfor the nonequilibrium state of those solutions is proposed, in which the slowest relaxationprocess is associated with the destruction of new phase nuclei. The process of their destructionis described in the framework of both the Lagrangian formalism with low dissipation and thenucleation theory. The self-diffusion coefficients of molecules from the nucleus surface arecalculated and used to estimate the lifetime of nuclei and its dependence on the nucleus size. Arelation between the diffusion coefficient of nuclei in the nucleus-size space and the coefficientof molecular self-diffusion from the nucleus surface is found. A comparison with availableexperimental data is made.

International audience; The paper reports the study of the photoinduced high spin (HS) state lifetime in a multistep spin crossover compound. Despite the pronounced three-step transition of the [Fe(dpsme)Pt(CN)4]·2/3dpsme·xEtOH·yH2O {dpsme = 4,4′-di(pyridylthio)methane; EtOH = ethanol} 3D compound, neither the T(LIESST) nor the relaxation kinetics exhibits stepwise features. From the detailed investigation (experiments and simulations) of these relaxations and the observation of the light-induced thermal hysteresis, a phase transition around 58 K is suspected.

A review of the new approach to the understanding of the structural relaxation of metallic glasses based on the interstitialcy theory has been presented. The key hypothesis of this theory proposed by Granato consists of the statement that the thermodynamic properties of crystalline, liquid and glassy states are closely related to the interstitial defects in the dumbbell (split) configuration, called also interstitialcies. It has been argued that structural relaxation of metallic glasses takes place through a change of the concentration of interstitialcy defects frozen-in from the melt upon glass production. Because of a strong interstitialcy-induced shear softening, the defect concentration can be precisely monitored by measurements of the unrelaxed shear modulus. Depending on the relation between the current interstitialcy concentration c and interstitialcy concentration in the metastable equilibrium, different types of structural relaxation (decreasing or increasing c) can be observed. It has been shown that this approach leads to a correct description of the relaxation kinetics at different testing conditions, heat effects occurring upon annealing, shear softening and a number of other structural relaxation-induced phenomena in metallic glasses. An intrinsic relation of these phenomena with the anharmonicity of the interatomic interaction has been outlined. A generalized form of the interstitialcy approach has been reviewed.

Objective: Pediatric patients with heart failure, compared to adults, respond differently to current armamentarium of heart failure (HF) therapeutics, indicating differences in the hearts of children and adults. We examined myofibril mechanics in children and adults with and without HF to determine: 1) baseline myofibril characteristics, 2) differences between children and adults, and 3) myofibril mechanics in the setting of HF. Methods: Myofibrils were obtained from pediatric and adult patients with IDC undergoing cardiac transplantation. Unused donor hearts were used as non-failing control (NF). Written informed consent was obtained. Myofibrils were stretched from slack length and set 5-10% above slack sarcomere length (SL), and Ca 2+ -activated and relaxed at 15°C. Mechanical and kinetic parameters: maximal tension (T max , mN/mm 2 ); rate constant of tension development ( k ACT , S -1 ); duration of slow relaxation phase ( t LIN , mSec), rate constant of fast phase relaxation ( k REL , S -1 ). Mechanical parameters ± SEM are shown. Results: Compared to NF adults, myofibrils from NF pediatric hearts had shorter SL (2.04±0.01 μm vs 2.11±0.01, p < 0.0001), slower t LIN (202.7+9.0 msec vs 152.9+4.1, p < 0.0001) and slower k REL (7.8+0.4 S -1 vs 15.7+0.8, p < 0.0001). T max and k ACT were similar. In the adult cohort, myofibrils from adult IDC patients showed slower k ACT (0.45+0.02 S -1 vs 0.57+0.03, p < 0.005) and slower k REL (11.9+0.7 S -1 vs 15.7+0.8, p < 0.005). T max and t LIN were similar. In the pediatric cohort, myofibrils from IDC developed lower T max (35.3+2.5 mN/mm 2 vs 57.5+4.4, p < 0.0001), and faster t LIN (136.6+3.2 msec vs 202.3+8.9, p < 0.0001) and faster k REL (9.1+0.4 S -1 vs 7.8+0.4, p < 0.05). k ACT was similar. Conclusion: NF myofibrils from children have shorter resting SL and slower relaxation kinetics than NF adults. While myofibrils from adults IDC result in slower activation and exponential relaxation kinetics, children with IDC display faster relaxation kinetic and reduced tension generation. These results show that myofibrils from children have fundamental differences in mechanical characteristics at baseline and in the setting of heart failure.

A comparative study of fluorescence relaxation kinetics of σ-conjugated poly(methylphenylsilane) (PMPS) polymer film and nanocomposites has been performed by ultrafast time-gated fluorescence measurements at various temperatures. Investigations have revealed a fine structure of excitonic σ-σ* band. We attribute this structure to emission from two spatially independent states with different ordering of the polymer chain segments, type gauche and trans conformations. In contrary to a more ordered polymer poly(di-n-hexylsilane), no clear thermochromic transition has been detected in PMPS film; however, the trans band intensity increases with temperature and with excitation wavelength, but it is absent when polymer is incorporated into nanopores of small diameter.

Accepted: 2009-11-20, 資料番号: SA1000724000

A series of 72-hour growth inhibition tests with green alga Desmodesmus (Scenedesmus) subspicatus (ISO 8692) has been performed to test the delayed fluorescence (DF) parameters as possible endpoint measurements. Sensitivity to five toxicants with direct and indirect effects on photosynthesis was tested, and the median effective concentration (EC50) values derived from the cell concentration, absorbance and DF were compared. The sensitivity of DF intensity (DFI) was comparable with the two endpoints suggested in ISO 8692 for all five toxicants: potassium dichromate, 3,5-dichlorophenol (3,5-DCP), DCMU, copper and cadmium. In the case of potassium dichromate and copper, DFI was more sensitive than the other endpoints in this study. The analysis of DF relaxation kinetics showed a specific response to the herbicide DCMU. Additionally, a 24-hour test was performed with the same toxicant concentrations (except copper), where DFI was measured 30 minutes, one hour and 24 hours after the exposure. The influence of toxicants on DFI after a 24-hour exposure was comparable with the effects after 72 hours. Only 3,5-DCP influenced DFI after 30 minutes. DF proved to be a simple, reliable and rapid measurement to assess toxicity in algal tests, which can to some extent differentiate among various toxicants.

We employed single myofibril techniques to test whether the presence of slow skeletal troponin-I (ssTnI) is sufficient to induce increased myofilament calcium sensitivity (EC50) and whether modulation of EC50 affects the dynamics of force development. Studies were performed using rabbit psoas myofibrils activated by rapid solution switch and in which Tn was partially replaced for either recombinant cardiac Tn(cTn) or Tn composed of recombinant cTn-T (cTnT) and cTn-C (cTnC), and recombinant ssTnI (ssTnI-chimera Tn). Tn exchange was performed in rigor solution (0.5 mg/ml Tn; 20°C; 2 h) and confirmed by SDS-PAGE. cTnI exchange induced a decrease in EC50; ssTnI-chimera Tn exchange induced a further decrease in EC50 (in μM: endogenous Tn, 1.35 ± 0.08; cTnI, 1.04 ± 0.13; ssTnI-chimera Tn, 0.47 ± 0.03). EC50 was also decreased by application of 100 μM bepridil (control: 2.04 ± 0.03 μM; bepridil 1.35 ± 0.03 μM). Maximum tension was not different between any groups. Despite marked alterations in EC50, none of the dynamic activation-relaxation parameters were affected under any condition. Our results show that 1) incorporation of ssTnI into the fast skeletal sarcomere is sufficient to induce increased myofilament Ca2+ sensitivity, and 2) the dynamics of actin-myosin interaction do not correlate with EC50. This result suggests that intrinsic cross-bridge cycling rate is not altered by the dynamics of thin-filament activation.

The kinetics of adsorption of lysozyme and a-lactalbumin from aqueous solution on silica and hydrophobized silica has been studied. The initial rate of adsorption of lysozyme at the hydrophilic surface is comparable with the limiting flux. For lysozyme at the hydrophobic surface and a-lactalbumin on both surfaces, the rate of adsorption is lower than the limiting flux, but the adsorption proceeds cooperatively, as manifested by an increase in the adsorption rate after the first protein molecules are adsorbed. At the hydrophilic surface, adsorption saturation (reflected in a steady-state value of the adsorbed amount) of both proteins strongly depends on the rate of adsorption, but for the hydrophobic surface no such dependency is observed. It points to structural relaxation ("spreading") of the adsorbed protein molecules, which occurs at the hydrophobic surface faster than at the hydrophilic one. For lysozyme, desorption has been studied as well. It is found that the desorbable fraction decreases after longer residence time of the protein at the interface. (C) 2006 Elsevier B.V. All rights reserved.

In the reaction A + B C, where A and B are ionic reactants having opposite charges, a B molecule approaching an A will experience a switching of the interaction potential when the A molecule is captured by one of the other B molecules in the medium. In the reversible case, the former B molecule still has a chance to react with the A, so that one needs to take into account the switched interaction between the reactant B and the product C as well as that between the reactants to treat the kinetics accurately. It is shown that this kind of interaction potential switching affects the relaxation kinetics in an intriguing way as observed in a recent experiment on an excited-state proton transfer reaction.

The structural relaxation, glass transition and crystallization processes of Mg65Cu25Y10 metallic glass are studied by Differential Scanning Calorimetry (DSC) and Mechanical spectroscopy. The relaxation model derived from the mechanical measurements is compared with the kinetics of these transformations obtained from the DSC curves. The structural relaxation kinetics is found to be controlled by the glassy dynamics following an Adams-Gibbs-Vogel function. The glass transition and crystallization kinetics are controlled by the dynamics of the supercooled melt following a Vogel-Fulcher-Tammann behaviour. The results suggest that the microscopic processes responsible of structural relaxation and aging below the glass transition correspond to the same processes generating the a-relaxation peak. (C) 2013 Elsevier B.V. All rights reserved.

We study the relaxation kinetics of reversible reactions of the type A + B ⇄ C + B by applying the many-particle kernel theory, which we have developed to investigate many-particle effects on general diffusion-influencedreactions. It is shown that for the target model, where A and C molecules are immobile and their interconversion is induced by the encounter with the B molecules that are present in much excess, the many-particle kernel theory gives a result that coincides with the known exact result.

Divalent europium doped strontium di-aluminate (SrAl4O 7 : Eu2+) nanocrystals have been synthesized using a facile sol-gel polymer thermolysis method. The photoluminescence characteristics of smaller particles (� ? 15 nm) show a significant difference with respect to their bulk counterpart. In this nanocrystalline system, the electronic structure of the Eu2+ excited state seems to undergo considerable modification induced by the surface states involved in slow relaxation kinetics that mimic phosphorescence like features.

A hybridized calculation of Phase Field Method and Cluster Variation Method is applied to investigate the relaxation process of Long-Range-Order parameter (LRO) originating from competitive growth of ordered domains. It is shown that the coarsening process proceeds by both the curvature-driven growth and coalescence among in-phase ordered domains. In the early annealing period, an average radius of ordered domains increases proportional to t 1/2 as predicted by the curvature-driven growth. In the later period, however, a deviation from this relation is manifested by coalescence process. The LRO relaxation kinetics largely depends on the frequency of coalescence event.

Phosphorylation of troponin I by protein kinase A (PKA) reduces Ca(2+) sensitivity and increases the rate of Ca(2+) release from troponin C and the rate of relaxation in cardiac muscle. In vitro experiments indicate that mutations that cause dilated cardiomyopathy (DCM) uncouple this modulation, but this has not been demonstrated in an intact contractile system. Using a Ca(2+)-jump protocol, we measured the effect of the DCM-causing mutation ACTC E361G on the equilibrium and kinetic parameters of Ca(2+) regulation of contractility in single transgenic mouse heart myofibrils. We used propranolol treatment of mice to reduce the level of troponin I and myosin binding protein C (MyBP-C) phosphorylation in their hearts before isolating the myofibrils. In nontransgenic mouse myofibrils, the Ca(2+) sensitivity of force was increased, the fast relaxation phase rate constant, kREL, was reduced, and the length of the slow linear phase, tLIN, was increased when the troponin I phosphorylation level was reduced from 1.02 to 0.3 molPi/TnI (EC50 P/unP = 1.8 ± 0.2, p < 0.001). Native myofibrils from ACTC E361G transgenic mice had a 2.4-fold higher Ca(2+) sensitivity than nontransgenic mouse myofibrils. Strikingly, the Ca(2+) sensitivity and relaxation parameters of ACTC E361G myofibrils did not depend on the troponin I phosphorylation level (EC50 P/unP = 0.88 ± 0.17, p = 0.39). Nevertheless, modulation of the Ca(2+) sensitivity of ACTC E361G myofibrils by sarcomere length or EMD57033 was indistinguishable from that of nontransgenic myofibrils. Overall, EC50 measured in different conditions varied over a 7-fold range. The time course of relaxation, as defined by tLIN and kREL, was correlated with EC50 but varied by just 2.7- and 3.3-fold, respectively. Our results confirm that troponin I phosphorylation specifically alters the Ca(2+) sensitivity of isometric tension and the time course of relaxation in cardiac muscle myofibrils. Moreover, the DCM-causing mutation ACTC E361G blunts this phosphorylation-dependent response without affecting other parameters of contraction, including length-dependent activation and the response to EMD57033.

International audience; The control over DNA elongation in nanofluidic devices holds great potential for large-scale genomic analysis. So far, the manipulation of DNA in nanochannels has been mostly carried out with electrophoresis and seldom with hydrodynamics, although the physics of soft matter in nanoscale flows has raised considerable interest over the past decade. In this report the migration of DNA is studied in nanochannels of lateral dimension spanning 100 to 500 nm using both actuation principles. We show that the relaxation kinetics are 3-fold slowed down and the extension increases up to 3-fold using hydrodynamics. We propose a model to account for the onset in elongation with the flow, which assumes that DNA response is determined by the shear-driven lift forces mediated by the proximity of the channels' walls. Overall, we suggest that hydrodynamic actuation allows for an improved manipulation of DNA in nanochannels.

A unifying theoretical framework for analyzing stochastic data from single-particle tracking (SPT) in viscoelastic materials is presented. A generalization of the bead-spring model for linear polymers is developed from a molecular point of view and from the standpoint of phenomenological linear viscoelasticity. The hydrodynamic interaction in the former is identified as the dashpots in the latter. In elementary terms, the intimate correspondence between time-correlation of the fluctuation measurements and transient relaxation kinetics after perturbation is discussed, and the central role of the fluctuation-dissipation relation is emphasized. The work presented here provides a bridge between the microscopic and the macroscopic views of linear viscoelastic biological materials, and is applicable to membrane protein diffusion, linear DNA chain dynamics, and mechanics of intracellular cytoskeletal networks.

Logarithmic oscillations superimposed on the temporal relaxation patterns of complex systems are considered from the standpoint of their hierarchical origin. We propose that a closer examination of experimental data should reveal logarithmic oscillations in systems that are characterized by a hierarchical structure of their dynamical degrees of freedom. On that footing, a new methodology of data analysis is proposed that may prove important for the dynamics of protein folding and of conformational fluctuations in proteins in which the relevant time scales of the dynamical evolution underlying the relaxation kinetics can be deduced from these oscillations.

Two competing and mutually exclusive mechanisms of ligand recognition - conformational selection and induced fit - have dominated our interpretation of ligand binding in biological macromolecules for almost six decades. Conformational selection posits the pre-existence of multiple conformations of the macromolecule from which the ligand selects the optimal one. Induced fit, on the other hand, postulates the existence of conformational rearrangements of the original conformation into an optimal one that are induced by binding of the ligand. In the former case, conformational transitions precede the binding event; in the latter, conformational changes follow the binding step. Kineticists have used a facile criterion to distinguish between the two mechanisms based on the dependence of the rate of relaxation to equilibrium, kobs, on the ligand concentration, [L]. A value of kobs decreasing hyperbolically with [L] has been seen as diagnostic of conformational selection, while a value of kobs increasing hyperbolically with [L] has been considered diagnostic of induced fit. However, this simple conclusion is only valid under the rather unrealistic assumption of conformational transitions being much slower than binding and dissociation events. In general, induced fit only produces values of kobs that increase with [L] but conformational selection is more versatile and is associated with values of kobs that increase with, decrease with or are independent of [L]. The richer repertoire of kinetic properties of conformational selection applies to kinetic mechanisms with single or multiple saturable relaxations and explains the behavior of nearly all experimental systems reported in the literature thus far. Conformational selection is always sufficient and often necessary to account for the relaxation kinetics of ligand binding to a biological macromolecule and is therefore an essential component of any binding mechanism. On the other hand, induced fit is never necessary and only sufficient in a few cases. Therefore, the long assumed importance and preponderance of induced fit as a mechanism of ligand binding should be reconsidered.