On the characterization of protein native state ensembles.


:Describing and understanding the biological function of a protein requires a detailed structural and thermodynamic description of the protein's native state ensemble. Obtaining such a description often involves characterizing equilibrium fluctuations that occur beyond the nanosecond timescale. Capturing such fluctuations remains nontrivial even for very long molecular dynamics and Monte Carlo simulations. We propose a novel multiscale computational method to exhaustively characterize, in atomistic detail, the protein conformations constituting the native state with no inherent timescale limitations. Applications of this method to proteins of various folds and sizes show that thermodynamic observables measured as averages over the native state ensembles obtained by the method agree remarkably well with nuclear magnetic resonance data that span multiple timescales. By characterizing equilibrium fluctuations at atomistic detail over a broad range of timescales, from picoseconds to milliseconds, our method offers to complement current simulation techniques and wet-lab experiments and can impact our understanding and description of the relationship between protein flexibility and function.


Biophys J


Biophysical journal


Shehu A,Kavraki LE,Clementi C




Has Abstract


2007-03-01 00:00:00














  • Changes in force and stiffness during stretch of skeletal muscle fibers, effects of hypertonicity.

    abstract::Slow stretch ramps (velocity: 0.17 fiber lengths s-1) were imposed during fused tetanic contractions of intact muscle fibers of the frog (1.4-3.0 degrees C; sarcomere length: 2.12-2.21 microns). Instantaneous force-extension relations were derived both under isometric conditions and during slow stretch by applying fas...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Månsson A

    更新日期:1989-08-01 00:00:00

  • Conformation and free energy analyses of the complex of calcium-bound calmodulin and the Fas death domain.

    abstract::Previous studies have demonstrated a calcium-dependent interaction of calmodulin (CaM) and Fas that is regulated during Fas-induced apoptosis in several cell lines, including cholangiocarcinoma, Jurkat cells, and osteoclasts. The binding of CaM and Fas has been identified on residues 231-254 of Fas; the V254N point mu...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Suever JD,Chen Y,McDonald JM,Song Y

    更新日期:2008-12-15 00:00:00

  • Dissecting the contribution of diffusion and interactions to the mobility of nuclear proteins.

    abstract::Quantitative characterization of protein interactions under physiological conditions is vital for systems biology. Fluorescence photobleaching/activation experiments of GFP-tagged proteins are frequently used for this purpose, but robust analysis methods to extract physicochemical parameters from such data are lacking...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Beaudouin J,Mora-Bermúdez F,Klee T,Daigle N,Ellenberg J

    更新日期:2006-03-15 00:00:00

  • Hydrodynamic properties of human erythrocyte band 3 solubilized in reduced Triton X-100.

    abstract::The oligomeric state and function of band 3, purified by sulfhydryl affinity chromatography in reduced Triton X-100, was investigated. Size exclusion high-performance liquid chromatography showed that a homogeneous population of band 3 dimers could be purified from whole erythrocyte membranes. The elution profile of b...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Taylor AM,Boulter J,Harding SE,Cölfen H,Watts A

    更新日期:1999-04-01 00:00:00

  • Molecular dynamics of alamethicin transmembrane channels from open-channel current noise analysis.

    abstract::Conductance noise measurement of the open states of alamethicin transmembrane channels reveals excess noise attributable to cooperative low-frequency molecular dynamics that can generate fluctuations approximately 1 A rms in the effective channel pore radius. Single-channel currents through both persistent and nonpers...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Mak DO,Webb WW

    更新日期:1995-12-01 00:00:00

  • Flux-concentration duality in dynamic nonequilibrium biological networks.

    abstract::The structure of dynamic states in biological networks is of fundamental importance in understanding their function. Considering the elementary reaction structure of reconstructed metabolic networks, we show how appreciation of a gradient matrix, G =dv/dx (where v is the vector of fluxes and x is the vector of concent...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Jamshidi N,Palsson BØ

    更新日期:2009-09-02 00:00:00

  • Lateral diffusion in an archipelago. Dependence on tracer size.

    abstract::In a pure fluid-phase lipid, the dependence of the lateral diffusion coefficient on the size of the diffusing particle may be obtained from the Saffman-Delbrück equation or the free-volume model. When diffusion is obstructed by immobile proteins or domains of gel-phase lipids, the obstacles yield an additional contrib...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Saxton MJ

    更新日期:1993-04-01 00:00:00

  • Class A Plexins Are Organized as Preformed Inactive Dimers on the Cell Surface.

    abstract::Plexins are single-pass transmembrane receptors that bind the axon guidance molecules semaphorins. Single-pass transmembrane proteins are an important class of receptors that display a wide variety of activation mechanisms, often involving ligand-dependent dimerization or conformational changes. Resolving the activati...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Marita M,Wang Y,Kaliszewski MJ,Skinner KC,Comar WD,Shi X,Dasari P,Zhang X,Smith AW

    更新日期:2015-11-03 00:00:00

  • Vibrational frequency shifts and relaxation rates for a selected vibrational mode in cytochrome C.

    abstract::The vibrational energy relaxation of a selected vibrational mode in cytochrome c--a C-D stretch in the terminal methyl group of Met80--has been studied using equilibrium molecular dynamics simulation and normal mode analysis methods. As demonstrated in the pioneering work of Romesberg and co-workers, isotopic labeling...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Bu L,Straub JE

    更新日期:2003-09-01 00:00:00

  • Sodium dodecyl sulfate-resistant complexes of Alzheimer's amyloid beta-peptide with the N-terminal, receptor binding domain of apolipoprotein E.

    abstract::Immunocytochemical, biochemical, and molecular genetic studies indicate that apolipoprotein E (apoE) plays an important role in the process of amyloidogenesis-beta. However, there is still no clear translation of these data into the pathogenesis of amyloidosis-beta. Previous studies demonstrated sodium dodecyl sulfate...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Golabek AA,Kida E,Walus M,Perez C,Wisniewski T,Soto C

    更新日期:2000-08-01 00:00:00

  • Nonlinear Elasticity of the ECM Fibers Facilitates Efficient Intercellular Communication.

    abstract::Biological cells embedded in fibrous matrices have been observed to form intercellular bands of dense and aligned fibers through which they mechanically interact over long distances. Such matrix-mediated cellular interactions have been shown to regulate various biological processes. This study aimed to explore the eff...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Sopher RS,Tokash H,Natan S,Sharabi M,Shelah O,Tchaicheeyan O,Lesman A

    更新日期:2018-10-02 00:00:00

  • Rotational dynamics of spin-labeled F-actin during activation of myosin S1 ATPase using caged ATP.

    abstract::The most probable source of force generation in muscle fibers in the rotation of the myosin head when bound to actin. This laboratory has demonstrated that ATP induces microsecond rotational motions of spin-labeled myosin heads bound to actin (Berger, C. L. E. C. Svensson, and D. D. Thomas. 1989. Proc. Natl. Acad. Sci...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Ostap EM,Thomas DD

    更新日期:1991-06-01 00:00:00

  • Order in phospholipid Langmuir-Blodgett monolayers determined by total internal reflection fluorescence.

    abstract::Orientational order parameters of two diphenylhexatriene (DPH)-based fluorescent probes, 2-(3-(diphenylhexatrienyl)propanoyl)-1-hexadecanoyl-sn-glycero-3-p hosphocholine (DPHpPC) and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), in dipalmitoylphosphatidylcholine (DPPC) Langmuir-Blodgett monolayers...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Zhai X,Kleijn JM

    更新日期:1997-06-01 00:00:00

  • Late events in the photocycle of bacteriorhodopsin mutant L93A.

    abstract::In the photocycle of bacteriorhodopsin (bR) from Halobacterium salinarum mutant L93A, the O-intermediate accumulates and the cycling time is increased approximately 200 times. Nevertheless, under continuous illumination, the protein pumps protons at near wild-type rates. We excited the mutant L93A in purple membrane w...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Tóth-Boconádi R,Keszthelyi L,Stoeckenius W

    更新日期:2003-06-01 00:00:00

  • Structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement of x-ray and neutron diffraction data. II. Distribution and packing of terminal methyl groups.

    abstract::We continue in this paper the presentation of theoretical and experimental methods for the joint refinement of neutron and x-ray lamellar diffraction data for the analysis of fluid (L alpha phase) bilayer structure (Wiener, M. C., and S. H. White. 1991 a, b, c. Biophys. J. 59:162-173 and 174-185; Biochemistry. 30:6997...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Wiener MC,White SH

    更新日期:1992-02-01 00:00:00

  • Channel properties of the purified acetylcholine receptor from Torpedo californica reconstituted in planar lipid bilayer membranes.

    abstract::The electrophysiological properties of the cation channel of the purified nicotinic acetylcholine receptor (AChR) reconstituted in planar lipid bilayers were characterized. Single-channel currents were activated by acetylcholine, carbamylcholine and suberyldicholine. The single channel conductance (28 pS in 0.3 M NaCl...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Montal M,Labarca P,Fredkin DR,Suarez-Isla BA

    更新日期:1984-01-01 00:00:00

  • Molecular dynamics in mouse atrial tumor sarcoplasmic reticulum.

    abstract::We have determined directly the effects of the inhibitory peptide phospholamban (PLB) on the rotational dynamics of the calcium pump (Ca-ATPase) of cardiac sarcoplasmic reticulum (SR). This was accomplished by comparing mouse ventricular SR, which has PLB levels similar to those found in other mammals, with mouse atri...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Voss JC,Mahaney JE,Jones LR,Thomas DD

    更新日期:1995-05-01 00:00:00

  • Diffusion and redistribution of lipid-like molecules between membranes in virus-cell and cell-cell fusion systems.

    abstract::The kinetics of redistribution of lipid-like molecules between the membranes of two fused spherical vesicles is studied by solving the time-dependent diffusion equation of the system. The effects on the probe redistribution rate of pore size at the fusion junction and the relative sizes of the vesicles are examined. I...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Rubin RJ,Chen YD

    更新日期:1990-11-01 00:00:00

  • A simulation of human heart function.

    abstract::A simulation of the function of the human heart and heart muscle has been developed in the form of a digital computer code. For a given set of values for the input variables, realistic values of the cardiac output variables are predicted. A detailed discussion of the simulation and some results obtained from its appli...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Hanna WT

    更新日期:1973-07-01 00:00:00

  • Study of the Expression Transition of Cardiac Myosin Using Polarization-Dependent SHG Microscopy.

    abstract::Detection of the transition between the two myosin isoforms α- and β-myosin in living cardiomyocytes is essential for understanding cardiac physiology and pathology. In this study, the differences in symmetry of polarization spectra obtained from α- and β-myosin in various mammalian ventricles and propylthiouracil-tre...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Yuan C,Zhao X,Wang Z,Borg TK,Ye T,Khalpey ZI,Runyan RB,Shao Y,Gao BZ

    更新日期:2020-03-10 00:00:00

  • Pulsed electron spin resonance resolves the coordination site of Cu²(+) ions in α1-glycine receptor.

    abstract::Herein, we identify the coordination environment of Cu²(+) in the human α1-glycine receptor (GlyR). GlyRs are members of the pentameric ligand-gated ion channel superfamily (pLGIC) that mediate fast signaling at synapses. Metal ions like Zn²(+) and Cu²(+) significantly modulate the activity of pLGICs, and metal ion co...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Ruthstein S,Stone KM,Cunningham TF,Ji M,Cascio M,Saxena S

    更新日期:2010-10-20 00:00:00

  • Random walk simulation of the MRI apparent diffusion coefficient in a geometrical model of the acinar tree.

    abstract::Apparent diffusion coefficient (ADC) measurement in the lung using gas magnetic resonance imaging is a promising technique with potential for reflecting changes in lung microstructure. Despite some recent impressive human applications, full interpretation of ADC measures remains an elusive goal, due to a lack of detai...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Pérez-Sánchez JM,Rodríguez I,Ruiz-Cabello J

    更新日期:2009-07-22 00:00:00

  • Growing yeast into cylindrical colonies.

    abstract::Microorganisms often form complex multicellular assemblies such as biofilms and colonies. Understanding the interplay between assembly expansion, metabolic yield, and nutrient diffusion within a freely growing colony remains a challenge. Most available data on microorganisms are from planktonic cultures, due to the la...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Vulin C,Di Meglio JM,Lindner AB,Daerr A,Murray A,Hersen P

    更新日期:2014-05-20 00:00:00

  • Thrust and Power Output of the Bacterial Flagellar Motor: A Micromagnetic Tweezers Approach.

    abstract::One of the most common swimming strategies employed by microorganisms is based on the use of rotating helical filaments, called flagella, that are powered by molecular motors. Determining the physical properties of this propulsive system is crucial to understanding the behavior of these organisms. Furthermore, the abi...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Pierce CJ,Osborne E,Mumper E,Lower BH,Lower SK,Sooryakumar R

    更新日期:2019-10-01 00:00:00

  • A kinetic assessment of the sequence of electron transfer from F(X) to F(A) and further to F(B) in photosystem I: the value of the equilibrium constant between F(X) and F(A).

    abstract::The x-ray structure analysis of photosystem I (PS I) crystals at 4-A resolution (Schubert et al., 1997, J. Mol. Biol. 272:741-769) has revealed the distances between the three iron-sulfur clusters, labeled F(X), F(1), and F(2), which function on the acceptor side of PS I. There is a general consensus concerning the as...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Shinkarev VP,Vassiliev IR,Golbeck JH

    更新日期:2000-01-01 00:00:00

  • Reactions between singlet oxygen and the constituents of nucleic acids. Importance of reactions in photodynamic processes.

    abstract::Bases, nucleosides, nucleotides, and polynucleotides were exposed to chemically generated singlet oxygen to determine whether the species oxidized paralleled those oxidized in photodynamic reactions. In neutral or basic aqueous solution guanine, guanosine, deoxyguanosine, guanylic acid, deoxyguanylic acid, thymine, an...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Hallett FR,Hallett BP,Snipes W

    更新日期:1970-04-01 00:00:00

  • Enantiomeric effects on excitation-contraction coupling in frog skeletal muscle by a chiral phenoxy carboxylic acid.

    abstract::Aromatic monocarboxylic acids are known to significantly potentiate the mechanical response of skeletal muscle fibers. In this study we investigated the effects of enantiomers of 2-(4-chlorophenoxy)propionic acid, chemically one of the simplest aromatic monocarboxylic acids with chiral properties, on mechanical thresh...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Heiny JA,Jong D,Bryant SH,Conte-Camerino D,Tortorella V

    更新日期:1990-01-01 00:00:00

  • Spreading of neutrophils: from activation to migration.

    abstract::Neutrophils rely on rapid changes in morphology to ward off invaders. Time-resolved dynamics of spreading human neutrophils after activation by the chemoattractant fMLF (formyl methionyl leucyl phenylalanine) was observed by RICM (reflection interference contrast microscopy). An image-processing algorithm was develope...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Sengupta K,Aranda-Espinoza H,Smith L,Janmey P,Hammer D

    更新日期:2006-12-15 00:00:00

  • Thermodynamic calculations for biochemical transport and reaction processes in metabolic networks.

    abstract::Thermodynamic analysis of metabolic networks has recently generated increasing interest for its ability to add constraints on metabolic network operation, and to combine metabolic fluxes and metabolite measurements in a mechanistic manner. Concepts for the calculation of the change in Gibbs energy of biochemical react...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Jol SJ,Kümmel A,Hatzimanikatis V,Beard DA,Heinemann M

    更新日期:2010-11-17 00:00:00

  • Free energies of molecular bound states in lipid bilayers: lethal concentrations of antimicrobial peptides.

    abstract::The lipid matrix, or the lipid bilayer, of cell membranes is a natural binding site for amphipathic molecules, including antimicrobial peptides, pore-forming proteins, and many drugs. The unique property of pore-forming antimicrobial peptides is that they exhibit a threshold concentration (called the lethal concentrat...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Huang HW

    更新日期:2009-04-22 00:00:00