Abstract:
:High-accuracy ab initio folding has remained an elusive objective despite decades of effort. To explore the folding landscape of villin headpiece subdomain HP35, we conducted two sets of replica exchange molecular dynamics for 200 ns each and three sets of conventional microsecond-long molecular dynamics simulations, using AMBER FF03 force field and a generalized-Born solvation model. The protein folded consistently to the native state; the lowest C(alpha)-rmsd from the x-ray structure was 0.46 A, and the C(alpha)- rmsd of the center of the most populated cluster was 1.78 A at 300 K. ab initio simulations have previously not reached this level. The folding landscape of HP35 can be partitioned into the native, denatured, and two intermediate-state regions. The native state is separated from the major folding intermediate state by a small barrier, whereas a large barrier exists between the major folding intermediate and the denatured states. The melting temperature T(m) = 339 K extracted from the heat-capacity profile was in close agreement with the experimentally derived T(m) = 342 K. A comprehensive picture of the kinetics and thermodynamics of HP35 folding emerges when the results from replica exchange and conventional molecular dynamics simulations are combined.
journal_name
Proc Natl Acad Sci U S Aauthors
Lei H,Wu C,Liu H,Duan Ydoi
10.1073/pnas.0608432104subject
Has Abstractpub_date
2007-03-20 00:00:00pages
4925-30issue
12eissn
0027-8424issn
1091-6490pii
0608432104journal_volume
104pub_type
杂志文章abstract::We have used X-ray diffraction on the rhombohedral phospholipid phase to reconstruct stalk structures in different pure lipids and lipid mixtures with unprecedented resolution, enabling a quantitative analysis of geometry, as well as curvature and hydration energies. Electron density isosurfaces are used to study shap...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1119442109
更新日期:2012-06-19 00:00:00
abstract::VEGF and angiopoietin-1 (Ang1) are two major angiogenic factors being investigated for the treatment of myocardial infarction (MI). Targeting VEGF and Ang1 expression in the ischemic myocardium can increase their local therapeutic effects and reduce possible adverse effects. Adeno-associated viral vectors (AAVs) expre...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1018925108
更新日期:2011-02-01 00:00:00
abstract::Productive T cell recognition of antigen-presenting cells (APCs) is normally accompanied by the formation of a cell-cell contact called the "immunological synapse." Our understanding of the steps leading up to this formation has been limited by the absence of tools for analyzing 3D surfaces and surface distributions a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.192573999
更新日期:2002-11-12 00:00:00
abstract::The enzymic activity of crystalline mitochondrial aspartate aminotransferase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) was determined in suspensions of noncrosslinked microcrystals in 30% (wt/vol) polyethylene glycol. The crystals (average dimensions, 22 x 5 x 0.8 micron) were small enough to preclude ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.7.1807
更新日期:1983-04-01 00:00:00
abstract::We present an automated laser tracking and optogenetic manipulation system (ALTOMS) for studying social memory in fruit flies (Drosophila melanogaster). ALTOMS comprises an intelligent central control module for high-speed fly behavior analysis and feedback laser scanning (∼40 frames per second) for targeting two lase...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1400997111
更新日期:2014-04-08 00:00:00
abstract::Unintended block of HERG K+ channels is a side effect of many common medications and is the most common cause of acquired long QT syndrome associated with increased risk of life-threatening arrhythmias. The molecular mechanism of high-affinity HERG block by structurally diverse compounds has been attributed to pi-stac...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.192367299
更新日期:2002-09-17 00:00:00
abstract::Intermediate filaments-cytoplasmic filaments with a diameter of 8-9 nm-have been described in a large variety of cell types. In this study, the subunit protein of the neurofilament and the presumptive subunit of the astroglial filament are compared by immunological and biochemical methods and are found to be very simi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.2.529
更新日期:1976-02-01 00:00:00
abstract::After exposure of segments of rabbit taenia coli to the nonionic detergent Triton X-100, tension could be induced by increasing the [Ca2+] in the micromolar range. In the presence of a saturating [Ca2+], this preparation developed nearly 100% of the control tetanus tension recorded from the intact muscle prior to the ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.7.3527
更新日期:1978-07-01 00:00:00
abstract::The management of harmful species, including invasive species, pests, parasites, and diseases, is a major global challenge. Harmful species cause severe damage to ecosystems, biodiversity, agriculture, and human health. In particular, managing harmful species often requires cooperation among multiple agents, such as l...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1917028117
更新日期:2020-05-12 00:00:00
abstract::Animals are associated with a microbiome that can affect their reproductive success. It is, therefore, important to understand how a host and its microbiome coevolve. According to the hologenome concept, hosts and their microbiome form an integrated evolutionary entity, a holobiont, on which selection can potentially ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1909790116
更新日期:2019-10-08 00:00:00
abstract::Increased intestinal permeability has been observed in numerous human autoimmune diseases, including type-1 diabetes (T1D) and its' animal model, the BB-wor diabetic prone rat. We have recently described zonulin, a protein that regulates intercellular tight junctions. The objective of this study was to establish wheth...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0500178102
更新日期:2005-02-22 00:00:00
abstract::Recent evidence indicates a specific role for vascular endothelial growth factor a (Vegfa) during artery development in both zebrafish and mouse embryos, whereas less is known about signals that govern vein formation. In zebrafish, loss of vegfa blocks segmental artery formation and reduces artery-specific gene expres...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0506886103
更新日期:2006-04-25 00:00:00
abstract::The voltage-sensor domain (VSD) of voltage-dependent ion channels and enzymes is critical for cellular responses to membrane potential. The VSD can also be regulated by interaction with intracellular proteins and ligands, but how this occurs is poorly understood. Here, we show that the VSD of the BK-type K(+) channel ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0705873104
更新日期:2007-11-13 00:00:00
abstract::Selective autophagy of damaged mitochondria requires autophagy receptors optineurin (OPTN), NDP52 (CALCOCO2), TAX1BP1, and p62 (SQSTM1) linking ubiquitinated cargo to autophagic membranes. By using quantitative proteomics, we show that Tank-binding kinase 1 (TBK1) phosphorylates all four receptors on several autophagy...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1523926113
更新日期:2016-04-12 00:00:00
abstract::RNA 3'-phosphate cyclase (RtcA) synthesizes RNA 2',3' cyclic phosphate ends via three steps: reaction with ATP to form a covalent RtcA-(histidinyl-Nε)-AMP intermediate; transfer of adenylate to an RNA 3'-phosphate to form RNA(3')pp(5')A; and attack of the vicinal O2' on the 3'-phosphorus to form a 2',3' cyclic phospha...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1115560108
更新日期:2011-12-27 00:00:00
abstract::Variation in the multiplication rate of blood stage malaria parasites is often positively correlated with the severity of the disease they cause. The rodent malaria parasite Plasmodium yoelii yoelii has strains with marked differences in multiplication rate and pathogenicity in the blood. We have used genetic analysis...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0811430106
更新日期:2009-04-28 00:00:00
abstract::Replication through damaged sites in DNA requires in Escherichia coli the SOS stress-inducible DNA polymerase V (UmuC), which is specialized for lesion bypass. Homologs of the umuC gene were found on native conjugative plasmids, which often carry multiple antibiotic-resistant genes. MucB is a UmuC homolog present on p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.200361997
更新日期:2000-10-10 00:00:00
abstract::Synthesis of mouse metallothionein (MT)-I and MT-II is transcriptionally induced by the synthetic glucocorticoid, dexamethasone (DEX) or both in vivo as well as in numerous cell lines. However, the location(s) of a glucocorticoid response element (GRE) has not been described. The observation that a marked MT-I gene, a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.19.10045
更新日期:1997-09-16 00:00:00
abstract::The M2 protein of influenza A virus forms a transmembrane proton channel important for viral infection and replication. Amantadine blocks this channel, thus inhibiting viral replication. Elucidating the high-resolution structure of the M2 protein and its change upon amantadine binding is crucial for designing antivira...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0711500105
更新日期:2008-02-05 00:00:00
abstract::Costimulation is required for optimal T cell activation, yet it is unclear whether poxviruses dedicatedly subvert costimulation during infection. Here, we report that the secreted M2 protein encoded by cowpox virus (CPXV) specifically interacts with human and murine B7.1 (CD80) and B7.2 (CD86). We also show that M2 co...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1909414116
更新日期:2019-10-15 00:00:00
abstract::We report an approach for the detection of magnetic resonance imaging without superconducting magnets and cryogenics: optical atomic magnetometry. This technique possesses a high sensitivity independent of the strength of the static magnetic field, extending the applicability of magnetic resonance imaging to low magne...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0605396103
更新日期:2006-08-22 00:00:00
abstract::Cell-based therapies, using multipotent mesenchymal stem cells (MSCs) for organ regeneration, are being pursued for cardiac disease, orthopedic injuries and biomaterial fabrication. The molecular pathways that regulate MSC-mediated regeneration or enhance their therapeutic efficacy are, however, poorly understood. We ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0803437105
更新日期:2008-11-25 00:00:00
abstract::It has been nearly 40 y since it was suggested that genomic methylation patterns could be transmitted via maintenance methylation during S phase and might play a role in the dynamic regulation of gene expression during development [Holliday R, Pugh JE (1975) Science 187(4173):226-232; Riggs AD (1975) Cytogenet Cell Ge...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.1415301111
更新日期:2015-06-02 00:00:00
abstract::Since at least the 1920s, it has been reported that common chimpanzees (Pan troglodytes) differ from humans in being capable of exceptional feats of "super strength," both in the wild and in captive environments. A mix of anecdotal and more controlled studies provides some support for this view; however, a critical re...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1619071114
更新日期:2017-07-11 00:00:00
abstract::In order to retain in an in situ system the control mechanisms involved in synthesis of bacteriophage T4 DNA, infected cells were made permeable to nucleotides by plasmolysis with concentrated sucrose. Such preparations use exogenous deoxyribonucleotides to synthesize T4 phage DNA. As has been observed with in vivo st...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.8.2196
更新日期:1973-08-01 00:00:00
abstract::Osteoclasts, bone-resorptive multinucleated cells derived from hematopoietic stem cells, are associated with many bone-related diseases, such as osteoporosis. Osteoclast-targeting small-molecule inhibitors are valuable tools for studying osteoclast biology and for developing antiresorptive agents. Here, we have discov...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0712239105
更新日期:2008-08-19 00:00:00
abstract::Peptidoglycan (PGN) recognition proteins (PGRPs) are pattern-recognition receptors of the innate immune system that bind and, in some cases, hydrolyze bacterial PGNs. We determined the crystal structure, at 2.30-A resolution, of the C-terminal PGN-binding domain of human PGRP-Ialpha in complex with a muramyl tripeptid...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0407856101
更新日期:2004-12-07 00:00:00
abstract::Vertebrate primary cilium is a Hedgehog signaling center but the extent of its involvement in other signaling systems is less well understood. This report delineates a mechanism by which fibroblast growth factor (FGF) controls primary cilia. Employing proteomic approaches to characterize proteins associated with the F...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1800338116
更新日期:2019-03-05 00:00:00
abstract::The guanosine hydrazide 1 yields a stable supramolecular hydrogel based on the formation of a guanine quartet (G-quartet) in presence of metal cations. The effect of various parameters (concentration, nature of metal ion, and temperature) on the properties of this gel has been studied. Proton NMR spectroscopy is shown...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0501663102
更新日期:2005-04-26 00:00:00
abstract::Eukaryotic DNA replication fidelity relies on the concerted action of DNA polymerase nucleotide selectivity, proofreading activity, and DNA mismatch repair (MMR). Nucleotide selectivity and proofreading are affected by the balance and concentration of deoxyribonucleotide (dNTP) pools, which are strictly regulated by r...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1618714114
更新日期:2017-05-30 00:00:00