Abstract:
:An automatic protein design procedure is used to select amino acid sequences that optimize the folding free energy function for a given protein. The only information used in designing the sequences is a set of known backbone structures for each protein, a rotamer library, and a well established classical empirical force field, which relies on basic physical chemical principles that underlie molecular interactions and protein stability, and has not been adjusted to yield native-like sequences. Applying the procedure to 7 different known protein folds, representing a total of 45 different native protein structures, yields ensembles of designed sequences displaying remarkable similarity to their natural counterparts in the protein core, but which are distinctly non-native on the protein surface. We show that natural and designed sequences for a given fold score significantly higher than random sequences against profiles derived from both, designed and natural sequence ensembles. Furthermore, we find that designed sequence profiles can be used to retrieve the native sequences for many of the analyzed proteins using standard PSI-BLAST searches in sequence databases. These findings may have important implications for our understanding the selection pressures operating on natural protein sequences and hold promise for improving fold recognition.
journal_name
Proc Natl Acad Sci U S Aauthors
Jaramillo A,Wernisch L,Héry S,Wodak SJdoi
10.1073/pnas.212068599keywords:
subject
Has Abstractpub_date
2002-10-15 00:00:00pages
13554-9issue
21eissn
0027-8424issn
1091-6490pii
212068599journal_volume
99pub_type
杂志文章abstract::The insulin signaling pathway is of pivotal importance in metabolic diseases, such as diabetes, and in cellular processes, such as aging. Insulin activates a tyrosine phosphorylation cascade that branches to create a complex network affecting multiple biological processes. To understand the full spectrum of the tyrosi...
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.0711713105
更新日期:2008-02-19 00:00:00
abstract::Extracts of wheat chloroplasts contain a poly(A) polymerase which can polymerize AMP residues from ATP onto an RNA primer. Whole extracts of wheat leaves also contain another poly(A) polymerase which is present in much larger amount and is probably derived from the nuclei. Both polymerases can utilize as primer poly(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.71.2.389
更新日期:1974-02-01 00:00:00
abstract::We report a measurement of the transverse momentum correlation between two photons by detecting only one of them. Our method uses two identical sources in an arrangement in which the phenomenon of induced coherence without induced emission is observed. In this way, we produce an interference pattern in the superpositi...
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.1620979114
更新日期:2017-02-14 00:00:00
abstract::The cell-surface antigen detected by the monoclonal antibody JONES is expressed in the retina and a number of other central nervous system regions of the rat during the latter part of embryonic development and the early postnatal period. In addition to the expression on certain neuroblast populations it is found on so...
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.84.23.8716
更新日期:1987-12-01 00:00:00
abstract::Smooth muscle cells (SMCs) have been shown to migrate in response to insulin-like growth factor I (IGF-I). However, the mechanism mediating this response has not been determined. The migration rates of porcine and human vascular SMCs were assessed in a monolayer wounding assay. IGF-I and IGF-II induced increases of 14...
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.93.6.2482
更新日期:1996-03-19 00:00:00
abstract::The TFIID transcription initiation complex is composed of TBP and multiple TAFs. Studies in unicellular systems indicate that TAF250 is required for progression through G(1)/S of the cell cycle and repression of apoptosis. Here we extend these in vivo studies by determining the developmental requirements for TAF250 in...
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.97.3.1154
更新日期:2000-02-01 00:00:00
abstract::The immunoglobulin light chain is thought to be organized into two structural domains, the constant and the variable regions, linked by a switch region of lesser tertiary organization. Light chains of homogeneous rabbit antibodies to pneumococcal polysaccharides labeled with (125)I were subjected to trypsin digestion ...
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.69.9.2495
更新日期:1972-09-01 00:00:00
abstract::Age-related hearing loss and noise-induced hearing loss are major causes of human morbidity. Here we used genetics and functional studies to show that a shared cause of these disorders may be loss of function of the ATP-gated P2X(2) receptor (ligand-gated ion channel, purinergic receptor 2) that is expressed in sensor...
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.1222285110
更新日期:2013-02-05 00:00:00
abstract::During neurogenesis of the mammalian neocortex, neural progenitor cells divide to generate daughter cells that either become neurons or remain as progenitor cells. The mouse numb (m-numb) gene encodes a membrane-associated protein that is asymmetrically localized to the apical cell membrane of dividing cortical progen...
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.97.12.6844
更新日期:2000-06-06 00:00:00
abstract::The TrkC neurotrophin receptor belongs to the functional dependence receptor family, members of which share the ability to induce apoptosis in the absence of their ligands. Such a trait has been hypothesized to confer tumor-suppressor activity. Indeed, cells that express these receptors are thought to be dependent on ...
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.1212333110
更新日期:2013-02-19 00:00:00
abstract::The H2O2-requiring ligninase of the basidiomycete Phanerochaete chrysosporium oxidatively cleaves both lignin and lignin model compounds between C alpha and C beta (C-1 and C-2) of their aliphatic side chains. Previous work has demonstrated a reaction mechanism by which ligninase oxidizes aromatic substrates to their ...
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.83.11.3708
更新日期:1986-06-01 00:00:00
abstract::Although it has been known for decades that the tight junctions of fluid-transporting epithelia are leaky to ions, it has not been possible to determine directly whether significant transjunctional water movement also occurs. An optical microscopic technique was developed for the direct visualization of the flow veloc...
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.95.11.6526
更新日期:1998-05-26 00:00:00
abstract::The importance of proper ion channel trafficking is underpinned by a number of channel-linked genetic diseases whose defect is associated with failure to reach the cell surface. Conceptually, it is reasonable to suggest that the function of ion channels depends critically on the precise subcellular localization and th...
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.0908207106
更新日期:2009-10-27 00:00:00
abstract::When rat pancreatic polynucleosomes were poly(ADP-ribosyl)ated with purified calf thymus poly(ADP-ribose) polymerase and examined by electron microscopy, a relaxation of their native zigzag structure was observed. At high ionic strengths control nucleosomes condensed into 250-A-thick fibers, but poly(ADP-ribosyl)ated ...
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.79.11.3423
更新日期:1982-06-01 00:00:00
abstract::Theoretical distributions of genetic distance between reproductively isolated taxa are derived by means of computer simulation, taking into account mutation and random genetic drift. The distributions obtained are in good agreement with the observed distributions of interracial and interspecific genetic distances for ...
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.72.7.2758
更新日期:1975-07-01 00:00:00
abstract::The positive transcription elongation factor b (P-TEFb) is involved in physiological and pathological events including inflammation, cancer, AIDS, and cardiac hypertrophy. The balance between its active and inactive form is tightly controlled to ensure cellular integrity. We report that the transcriptional repressor C...
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.1220136110
更新日期:2013-07-30 00:00:00
abstract::Cognitive flexibility depends on a fast neural learning mechanism for enhancing momentary relevant over irrelevant information. A possible neural mechanism realizing this enhancement uses fast spiking interneurons (FSIs) in the striatum to train striatal projection neurons to gate relevant and suppress distracting cor...
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.2001348117
更新日期:2020-07-28 00:00:00
abstract::The yeast auxiliary transcription factor GAL11, a candidate for the coactivator, was partially purified from yeast cells, and its function was characterized in a cell-free transcription system. The partially purified GAL11 protein stimulated basal transcription from the CYC1 core promoter by a factor of 4-5 at the ste...
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.90.18.8382
更新日期:1993-09-15 00:00:00
abstract::Multiple sclerosis is a chronic disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal loss. The immunopathogenesis of demyelination in multiple sclerosis involves an autoantibody response to myelin oligodendrocyte glycoprotein (MOG), a type I transmembrane protein located...
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.1133443100
更新日期:2003-08-05 00:00:00
abstract::Cells respond to mechanical forces whether applied externally or generated internally via the cytoskeleton. To study the cellular response to forces separately, we applied external forces to cells via microfabricated magnetic posts containing cobalt nanowires interspersed among an array of elastomeric posts, which act...
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.0611613104
更新日期:2007-09-11 00:00:00
abstract::Endothelial cells (EC) play a central role in inflammatory immune responses and efficiently induce effector functions in T cells, despite lacking the classical costimulatory ligands CD80 and CD86. By using the mAb HIL-131 we now demonstrate that human inducible costimulator-ligand (ICOS-L), a molecule related to CD80/...
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.092576699
更新日期:2002-04-30 00:00:00
abstract::A serumless, chemically defined medium has been developed for the culture of oligodendrocytes isolated from primary neonatal rat cerebral cultures. Combined together, insulin, transferrin, and fibroblast growth factor synergistically induced an essentially homogenous population (95-98%) of cells expressing glycerol-3-...
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.82.10.3509
更新日期:1985-05-01 00:00:00
abstract::Fibrosis is caused by scar tissue formation in internal organs and is associated with 45% of deaths in the United States. Two closely related human serum proteins, serum amyloid P (SAP) and C-reactive protein (CRP), strongly affect fibrosis. In multiple animal models, and in Phase 1 and Phase 2 clinical trials, SAP af...
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.1500956112
更新日期:2015-07-07 00:00:00
abstract::Understanding the causes and consequences of wildfires in forests of the western United States requires integrated information about fire, climate changes, and human activity on multiple temporal scales. We use sedimentary charcoal accumulation rates to construct long-term variations in fire during the past 3,000 y in...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.1112839109
更新日期:2012-02-28 00:00:00
abstract::Addition of antisense oligonucleotides to cell cultures has been used to specifically inhibit gene expression. We have investigated the mechanism by which oligonucleotides enter living cells. These compounds are taken up by cells in a saturable, size-dependent manner compatible with receptor-mediated endocytosis. Poly...
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.86.10.3474
更新日期:1989-05-01 00:00:00
abstract::Expression of amino acid biosynthesis genes in bacteria is often repressed when abundant supplies of the cognate amino acid are available. Repression of the Bacillus subtilis lysC gene by lysine was previously shown to occur at the level of premature termination of transcription. In this study we show that lysine dire...
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.2133705100
更新日期:2003-10-14 00:00:00
abstract::Bicistronic cassettes under control of a single promoter have recently been suggested as useful tools for coordinate expression of two different foreign proteins in mammalian cells. Using the long 5' untranslated region of encephalomyocarditis virus as translational enhancer of the second gene, a bicistronic unit comp...
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.91.8.3176
更新日期:1994-04-12 00:00:00
abstract::During the early evolution of life, 8-oxo-7,8-dihydro-2'-deoxyguanosine (O) may have functioned as a proto-flavin capable of repairing cyclobutane pyrimidine dimers in DNA or RNA by photoinduced electron transfer using longer wavelength UVB radiation. To investigate the ability of O to act as an excited-state electron...
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.1404411111
更新日期:2014-08-12 00:00:00
abstract::Voltage-dependent anion channels (VDACs) are pore-forming proteins (porins) that form the major pathway for movement of adenine nucleotides through the outer mitochondrial membrane. Electrophysiological studies indicate that VDAC-like channel activity is also prevalent in the cell membranes of many mammalian cells. Ho...
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.060242297
更新日期:2000-03-28 00:00:00
abstract::Genetic screening is the most powerful method through which to uncover gene function. It has been applied very successfully in lower organisms but seldom attempted in mammalian species because of their long generation time. In this study, we exploit RNA interference (RNAi) for its potential use in genetic screening in...
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.0511034103
更新日期:2006-02-14 00:00:00