Abstract:
: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.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Shehu A,Kavraki LE,Clementi Cdoi
10.1529/biophysj.106.094409subject
Has Abstractpub_date
2007-03-01 00:00:00pages
1503-11issue
5eissn
0006-3495issn
1542-0086pii
S0006-3495(07)70959-1journal_volume
92pub_type
杂志文章abstract::Pressure versus distance relations have been obtained for solid (gel) and neat (liquid-crystalline) phase uncharged lipid bilayers by the use of x-ray diffraction analysis of osmotically stressed monoglyceride aqueous dispersions and multilayers. For solid phase monoelaidin bilayers, the interbilayer repulsive pressur...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(89)82888-7
更新日期:1989-05-01 00:00:00
abstract::The determination of intracellular protein concentrations is a prerequisite for understanding protein interaction networks in systems biology. Today, protein quantification is based either on mass spectrometry, which requires large cell numbers and sophisticated measurement protocols, or on quantitative Western blotti...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2011.09.058
更新日期:2011-12-07 00:00:00
abstract::Effects of intracellular ionic strength on the isotonic contraction properties of both intact fibers and skinned fibers give insights into the cross-bridge mechanism, but presently there is fundamental disagreement in the results on the two fiber preparations. This paper, which studies the effects on contraction of va...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(84)84166-1
更新日期:1984-02-01 00:00:00
abstract::Sperm have generally been supposed to penetrate the zona pellucida surrounding the mammalian egg with the aid of a protease, acrosin. Difficulties associated with this view are discussed and an alternative, mechanical hypothesis introduced. The calculated force exerted by individual sperm is too small to permit the ru...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(84)84207-1
更新日期:1984-04-01 00:00:00
abstract::Annelids possess giant extracellular oxygen carriers that exhibit a hexagonal bilayer appearance and have molecular masses of approximately 3.5 MDa. By small angle x-ray scattering (SAXS), Eudistylia vancouverii chlorocruorin and Macrobdella decora hemoglobin were investigated in solution. On the basis of the experime...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.103.037929
更新日期:2004-08-01 00:00:00
abstract::Understanding protein phase behavior is important for purification, storage, and stable formulation of protein drugs in the biopharmaceutical industry. Glycoproteins, such as monoclonal antibodies (MAbs) are the most abundant biopharmaceuticals and probably the most difficult to crystallize among water-soluble protein...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.106.098293
更新日期:2007-07-15 00:00:00
abstract::Neurons communicate by releasing neurotransmitters that are stored in intracellular vesicular compartments. PC12 cells are frequently used as a model secretory cell line that is described to have two subpools of vesicles: small clear vesicles and dense core vesicles. We measured transmitter molecules released from ves...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2014.10.060
更新日期:2014-12-16 00:00:00
abstract::To the best of our knowledge, this is the first report on the structure of product-inhibited mammalian peroxidase. Lactoperoxidase is a heme containing an enzyme that catalyzes the inactivation of a wide range of microorganisms. In the presence of hydrogen peroxide, it preferentially converts thiocyanate ion into a to...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2008.09.019
更新日期:2009-01-01 00:00:00
abstract::In this article, we demonstrate the new method of pulsed interleaved excitation (PIE), which can be used to extend the capabilities of multiple-color fluorescence imaging, fluorescence cross-correlation spectroscopy (FCCS), and single-pair fluorescence resonance energy transfer (spFRET) measurements. In PIE, multiple ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.105.064766
更新日期:2005-11-01 00:00:00
abstract::The general formalism required to treat two-state sliding filament models of muscle contraction, including free energy considerations, is first reviewed and amplified. This formalism is then used to examine, and modify as needed, three models studied previously by Podolsky and Nolan, in which cross-bridge attachment-d...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(75)85823-1
更新日期:1975-04-01 00:00:00
abstract::To detect changes in capsid structure that occur when a preassembled bacteriophage T7 capsid both packages and cleaves to mature-size longer (concatameric) DNA, the kinetics and thermodynamics are determined here for the binding of the protein-specific probe, 1,1'-bi(4-anilino)naphthalene-5,5'-di-sulfonic acid (bis-AN...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(92)81724-1
更新日期:1992-11-01 00:00:00
abstract::With their longest dimension typically being less than 100 nm, molecular motors are significantly below the optical-resolution limit. Despite substantial advances in fluorescence-based imaging methodologies, labeling with beads remains critical for optical-trapping-based investigations of molecular motors. A key exper...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2016.05.015
更新日期:2016-06-21 00:00:00
abstract::The small mechanosensitive channel, MscS, is a part of the turgor-driven solute efflux system that protects bacteria from lysis in the event of osmotic downshift. It has been identified in Escherichia coli as a product of the orphan yggB gene, now called mscS (Levina et al., 1999, EMBO J. 18:1730). Here I show that th...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(02)75169-2
更新日期:2002-07-01 00:00:00
abstract::The products of MgATP hydrolysis bind to the nucleotide site of myosin and thus may be expected to inhibit the contraction of muscle fibers. We measured the effects of phosphate and MgADP on the isometric tensions and isotonic contraction velocities of glycerinated rabbit psoas muscle at 10 degrees C. Addition of phos...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(85)83837-6
更新日期:1985-11-01 00:00:00
abstract::The molecular basis of the activation of G-proteins by the G-protein coupled receptor for parathyroid hormone (PTH) is unknown. Employing a combination of NMR methods and computer-based structural refinement, structural features involved in the activation of Galpha(s) by the PTH receptor (PTH1R) have been determined. ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.106.094813
更新日期:2007-01-15 00:00:00
abstract::Influenza neuraminidase is an important drug target. Glycans are present on neuraminidase and are generally considered to inhibit antibody binding via their glycan shield. In this work, we studied the effect of glycans on the binding kinetics of antiviral drugs to the influenza neuraminidase. We created all-atom in si...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2020.10.024
更新日期:2020-12-01 00:00:00
abstract::Guanine-rich DNA repeat sequences located at the terminal ends of chromosomal DNA can fold in a sequence-dependent manner into G-quadruplex structures, notably the terminal 150-200 nucleotides at the 3' end, which occur as a single-stranded DNA overhang. The crystal structures of quadruplexes with two and four human t...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.107.120501
更新日期:2008-07-01 00:00:00
abstract::Thermal stability of proteins is crucial for both biotechnological and therapeutic applications. Rational protein engineering therefore frequently aims at increasing thermal stability by introducing stabilizing mutations. The accurate prediction of the thermodynamic consequences caused by mutations, however, is highly...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2010.01.051
更新日期:2010-05-19 00:00:00
abstract::Stabilization of the lipid bilayer membrane in red blood cells by its association with an underlying membrane-associated cytoskeleton has long been recognized as critical for proper red blood cell function. One of the principal connections between skeleton and bilayer is via linkages between band 3, the integral membr...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.108.129163
更新日期:2008-08-01 00:00:00
abstract::The absolute direction of the retinal chromophore of bacterio-rhodopsin relative to the membrane plane is investigated by using an optical second-harmonic interference technique. Compared with the known adsorbed geometry of free retinylidene Schiff base on a glass substrate, our data indicate the beta-ionone ring of t...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(89)82883-8
更新日期:1989-05-01 00:00:00
abstract::Segmentation of the Drosophila melanogaster embryo results from the dynamic establishment of spatial mRNA and protein patterns. Here, we exploit recent temporal mRNA and protein expression measurements on the full surface of the blastoderm to calibrate a dynamical model of the gap gene network on the entire embryo cor...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2011.05.060
更新日期:2011-07-20 00:00:00
abstract::Omega-3 polyunsaturated fatty acids (n-3 PUFA), enriched in fish oils, are increasingly recognized to have potential benefits for treating many human afflictions. Despite the importance of PUFA, their molecular mechanism of action remains unclear. One emerging hypothesis is that phospholipids containing n-3 PUFA acyl ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2012.06.016
更新日期:2012-07-18 00:00:00
abstract::Hybrid global optimization methods attempt to combine the beneficial features of two or more algorithms, and can be powerful methods for solving challenging nonconvex optimization problems. In this paper, novel classes of hybrid global optimization methods, termed alternating hybrids, are introduced for application as...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(03)74905-4
更新日期:2003-02-01 00:00:00
abstract::Molecular dynamics calculations demonstrated the conformational change in the prion protein due to Ala(117)-->Val mutation, which is related to Gerstmann-Sträussler-Sheinker disease, one of the familial prion diseases. Three kinds of model structures of human and mouse prion proteins were examined: (model 1) nuclear m...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(02)75615-4
更新日期:2002-05-01 00:00:00
abstract::In cardiac tissue, during partial blockade of the membrane sodium channels, or at high frequencies of excitation, inexcitable obstacles with sharp edges may destabilize the propagation of electrical excitation waves, causing the formation of self-sustained vortices and turbulent cardiac electrical activity. The format...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(96)79691-1
更新日期:1996-03-01 00:00:00
abstract::The effects of different cations on the hydrodynamic radius (RH) of a 48-bp synthetic DNA are measured by time-resolved fluorescence polarization anisotropy of intercalated ethidium. Relative statistical errors in RH are only approximately 1%. With increasing cation concentration, Na+ causes a small decrease in RH, Cs...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(94)80481-3
更新日期:1994-07-01 00:00:00
abstract::In this work we tested the hypothesis that transgenic sustained overexpression of IGF-1 prevents age-dependent decreases in charge movement and intracellular Ca(2+) in skeletal muscle fibers. To this end, short flexor digitorum brevis (FDB) muscle fibers from 5-7- and 21-24-month-old FVB (wild-type) and S1S2 (IGF-1 tr...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(02)75489-1
更新日期:2002-03-01 00:00:00
abstract::The functional diversity of gap junction intercellular channels arising from the large number of connexin isoforms is significantly increased by heterotypic interactions between members of this family. This is particularly evident in the rectifying behavior of Cx26/Cx32 heterotypic channels (. Proc. Natl. Acad. Sci. U...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(99)77129-8
更新日期:1999-12-01 00:00:00
abstract::Coliphage T4 was used as a model system to study the mechanism of biological inactivation produced by tritium decay. Experimentally, tritiated precursors were incorporated into phage DNA (thymidine-(3)H) or into phage protein ((3)H-amino acids). The ratio of killing efficiencies for decays originating in phage DNA to ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(68)86537-3
更新日期:1968-09-01 00:00:00
abstract::Using a combination of microelectrode measurements and high-power microscopy we have demonstrated that different Donnan potentials can be recorded from the A- and I-bands of glycerinated and chemically skinned muscles in rigor, so that the A-band fixed charge concentration exceeds the I-band fixed charge concentration...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(85)83760-7
更新日期:1985-07-01 00:00:00