Thermodynamic prediction of protein neutrality.

Abstract:

:We present a simple theory that uses thermodynamic parameters to predict the probability that a protein retains the wild-type structure after one or more random amino acid substitutions. Our theory predicts that for large numbers of substitutions the probability that a protein retains its structure will decline exponentially with the number of substitutions, with the severity of this decline determined by properties of the structure. Our theory also predicts that a protein can gain extra robustness to the first few substitutions by increasing its thermodynamic stability. We validate our theory with simulations on lattice protein models and by showing that it quantitatively predicts previously published experimental measurements on subtilisin and our own measurements on variants of TEM1 beta-lactamase. Our work unifies observations about the clustering of functional proteins in sequence space, and provides a basis for interpreting the response of proteins to substitutions in protein engineering applications.

authors

Bloom JD,Silberg JJ,Wilke CO,Drummond DA,Adami C,Arnold FH

doi

10.1073/pnas.0406744102

keywords:

subject

Has Abstract

pub_date

2005-01-18 00:00:00

pages

606-11

issue

3

eissn

0027-8424

issn

1091-6490

pii

0406744102

journal_volume

102

pub_type

杂志文章
  • Heparin- and sulfatide-binding peptides from the type I repeats of human thrombospondin promote melanoma cell adhesion.

    abstract::Peptides from the three type I repeats of human endothelial cell thrombospondin, containing the consensus sequence-Trp-Ser-Xaa-Trp-, bind to sulfated glycoconjugates including heparin and sulfatide. The peptides are potent inhibitors for the binding of thrombospondin, laminin, or apolipoprotein E to these ligands. 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.89.7.3040

    authors: Guo NH,Krutzsch HC,Nègre E,Vogel T,Blake DA,Roberts DD

    更新日期:1992-04-01 00:00:00

  • Synergistic anti-human immunodeficiency virus type 1 effect of hydroxamate compounds with 2',3'-dideoxyinosine in infected resting human lymphocytes.

    abstract::The cellular models generally used in the in vitro evaluation of anti-human immunodeficiency virus compounds are dividing cells. A model constituted by resting lymphocytes may more accurately reflect a drug's future efficacy in humans, since viral DNA synthesis is known to take place in quiescent cells, creating a res...

    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.91.23.11017

    authors: Malley SD,Grange JM,Hamedi-Sangsari F,Vila JR

    更新日期:1994-11-08 00:00:00

  • Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing.

    abstract::Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on 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.1406103111

    authors: Yu SC,Chan KC,Zheng YW,Jiang P,Liao GJ,Sun H,Akolekar R,Leung TY,Go AT,van Vugt JM,Minekawa R,Oudejans CB,Nicolaides KH,Chiu RW,Lo YM

    更新日期:2014-06-10 00:00:00

  • Substrate binding and catalysis by ribonuclease P from cyanobacteria and Escherichia coli are affected differently by the 3' terminal CCA in tRNA precursors.

    abstract::We have studied the effect of the 3' terminal CCA sequence in precursors of tRNAs on catalysis by the RNase P RNA or the holoenzyme from the cyanobacterium Synechocystis sp. PCC 6803 in a completely homologous system. We have found that the absence of the 3' terminal CCA is not detrimental to activity, which is in sha...

    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.96.12.6672

    authors: Pascual A,Vioque A

    更新日期:1999-06-08 00:00:00

  • Control of a Salmonella virulence operon by proline-charged tRNA(Pro).

    abstract::The intracellular pathogen Salmonella enterica serovar Typhimurium requires the mgtC gene to cause disease. The mgtC transcript includes a long leader region that harbors a short proline codon-rich ORF--termed mgtP--the translation of which is predicted to favor formation of one of two alternative stem-loop structures...

    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.1316209111

    authors: Lee EJ,Choi J,Groisman EA

    更新日期:2014-02-25 00:00:00

  • Magnetic circular dichroism of molecules in dense media: benzene.

    abstract::This paper presents some calculated results on the vibrational structuring of the magnetic circular dichroism of the benzene (1)A(1g)"(1)B(2u) transition. The good agreement between the experimental and calculated relative intensities of the B-bands (positive magnetic circular dichroism bands) indicates that these ban...

    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.69.8.2000

    authors: Shieh DJ,Lin SH,Eyring H

    更新日期:1972-08-01 00:00:00

  • Mouse model recapitulating human Fcγ receptor structural and functional diversity.

    abstract::The in vivo biological activities of IgG antibodies result from their bifunctional nature, in which antigen recognition by the Fab is coupled to the effector and immunomodulatory diversity found in the Fc domain. This diversity, resulting from both amino acid and glycan heterogeneity, is translated into cellular respo...

    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.1203954109

    authors: Smith P,DiLillo DJ,Bournazos S,Li F,Ravetch JV

    更新日期:2012-04-17 00:00:00

  • Experience-dependent coding of facial expression in superior temporal sulcus.

    abstract::Sensory information from the external world is inherently ambiguous, necessitating prior experience as a constraint on perception. Prolonged experience (adaptation) induces perception of ambiguous morph faces as a category different from the adapted category, suggesting sensitivity in underlying neural codes to differ...

    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.0702548104

    authors: Furl N,van Rijsbergen NJ,Treves A,Friston KJ,Dolan RJ

    更新日期:2007-08-14 00:00:00

  • Membrane optical activity: some facts and fallacies.

    abstract::The circular dichroism of hypothetical, water-filled, spherical shells, 75-3500 nm in radius, with walls 7.5 nm thick, composed of poly(L-lysine) in various conformational proportions, and suspended in water, were computed from the known optical properties of this polypeptide by classical general light-scattering theo...

    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.70.11.3235

    authors: Wallach DF,Low DA,Bertland AV

    更新日期:1973-11-01 00:00:00

  • Wnt signaling and a Smad pathway blockade direct the differentiation of human pluripotent stem cells to multipotent neural crest cells.

    abstract::Neural crest stem cells can be isolated from differentiated cultures of human pluripotent stem cells, but the process is inefficient and requires cell sorting to obtain a highly enriched population. No specific method for directed differentiation of human pluripotent cells toward neural crest stem cells has yet been 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.1113746108

    authors: Menendez L,Yatskievych TA,Antin PB,Dalton S

    更新日期:2011-11-29 00:00:00

  • Atomistic structure and dynamics of the human MHC-I peptide-loading complex.

    abstract::The major histocompatibility complex class-I (MHC-I) peptide-loading complex (PLC) is a cornerstone of the human adaptive immune system, being responsible for processing antigens that allow killer T cells to distinguish between healthy and compromised cells. Based on a recent low-resolution cryo-electron microscopy (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.2004445117

    authors: Fisette O,Schröder GF,Schäfer LV

    更新日期:2020-08-25 00:00:00

  • Immunotoxin SS1P is rapidly removed by proximal tubule cells of kidney, whose damage contributes to albumin loss in urine.

    abstract::Recombinant immunotoxins (RITs) are chimeric proteins composed of an Fv and a protein toxin being developed for cancer treatment. The Fv brings the toxin to the cancer cell, but most of the RITs do not reach the tumor and are removed by other organs. To identify cells responsible for RIT removal, and the pathway by wh...

    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.1919038117

    authors: Liu XF,Wei J,Zhou Q,Molitoris BA,Sandoval R,Kobayashi H,Okada R,Nagaya T,Karim B,Butcher D,Pastan I

    更新日期:2020-03-17 00:00:00

  • Recognition of female kin by male bees through olfactory signals.

    abstract::After males of Lasioglossum zephyrum (Hymenoptera: Halictidae) have first been exposed to a conspecific female, the attractiveness of a second female diminishes with increasing genealogical relationship between the two females. The most parsimonious explanation for this is a polygenically controlled female sex pheromo...

    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.80.14.4551

    authors: Smith BH

    更新日期:1983-07-01 00:00:00

  • Drivers and hotspots of extinction risk in marine mammals.

    abstract::The world's oceans are undergoing profound changes as a result of human activities. However, the consequences of escalating human impacts on marine mammal biodiversity remain poorly understood. The International Union for the Conservation of Nature (IUCN) identifies 25% of marine mammals as at risk of extinction, but ...

    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.1121469109

    authors: Davidson AD,Boyer AG,Kim H,Pompa-Mansilla S,Hamilton MJ,Costa DP,Ceballos G,Brown JH

    更新日期:2012-02-28 00:00:00

  • Tactile perception and working memory in rats and humans.

    abstract::Primates can store sensory stimulus parameters in working memory for subsequent manipulation, but until now, there has been no demonstration of this capacity in rodents. Here we report tactile working memory in rats. Each stimulus is a vibration, generated as a series of velocity values sampled from a normal distribut...

    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.1315171111

    authors: Fassihi A,Akrami A,Esmaeili V,Diamond ME

    更新日期:2014-02-11 00:00:00

  • Dynamic secretion during meiotic reentry integrates the function of the oocyte and cumulus cells.

    abstract::The differentiation of the female gamete into a developmentally competent oocyte relies on the protected environment of the ovarian follicle. The oocyte plays a key role in establishing this microenvironment by releasing paracrine factors that control the functions of surrounding somatic cells. Growth differentiation ...

    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.1519990113

    authors: Cakmak H,Franciosi F,Zamah AM,Cedars MI,Conti M

    更新日期:2016-03-01 00:00:00

  • Evolution of resistance in vitro reveals mechanisms of artemisinin activity in Toxoplasma gondii.

    abstract::Artemisinins are effective against a variety of parasites and provide the first line of treatment for malaria. Laboratory studies have identified several mechanisms for artemisinin resistance in Plasmodium falciparum, including mutations in Kelch13 that are associated with delayed clearance in some clinical isolates, ...

    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.1914732116

    authors: Rosenberg A,Luth MR,Winzeler EA,Behnke M,Sibley LD

    更新日期:2019-12-05 00:00:00

  • bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans.

    abstract::Very little is known about how animals discriminate pathogens from innocuous microbes. To address this question, we examined infection-response gene induction in the nematode Caenorhabditis elegans. We focused on genes that are induced in C. elegans by infection with the bacterial pathogen Pseudomonas aeruginosa, but ...

    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.0914643107

    authors: Estes KA,Dunbar TL,Powell JR,Ausubel FM,Troemel ER

    更新日期:2010-02-02 00:00:00

  • MAL6 of Saccharomyces: a complex genetic locus containing three genes required for maltose fermentation.

    abstract::The MAL6 locus is one of five closely related unlinked loci, any one of which is sufficient for fermentation of maltose in Saccharomyces. Previous genetic analysis indicated that this locus is defined by two complementation groups, MALp and MALg. MALp reportedly is a regulatory gene required for inducible synthesis of...

    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.81.9.2811

    authors: Needleman RB,Kaback DB,Dubin RA,Perkins EL,Rosenberg NG,Sutherland KA,Forrest DB,Michels CA

    更新日期:1984-05-01 00:00:00

  • roundabout4 is essential for angiogenesis in vivo.

    abstract::Stereotypical patterns of vascular and neuronal networks suggest that specific genetic programs tightly control path determination and, consequently, angiogenesis and axon-guidance mechanisms. Our study focuses on one member of the roundabout family of receptors, which traditionally mediate repulsion from the midline....

    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.0408318102

    authors: Bedell VM,Yeo SY,Park KW,Chung J,Seth P,Shivalingappa V,Zhao J,Obara T,Sukhatme VP,Drummond IA,Li DY,Ramchandran R

    更新日期:2005-05-03 00:00:00

  • ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release.

    abstract::Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by progressive ectopic mineralization of the skin, eyes, and arteries, for which no effective treatment exists. PXE is caused by inactivating mutations in the gene encoding ATP-binding cassette sub-family C member 6 (ABCC6), an ATP-dependen...

    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.1319582110

    authors: Jansen RS,Küçükosmanoglu A,de Haas M,Sapthu S,Otero JA,Hegman IE,Bergen AA,Gorgels TG,Borst P,van de Wetering K

    更新日期:2013-12-10 00:00:00

  • Multimodular biosensors reveal a novel platform for activation of G proteins by growth factor receptors.

    abstract::Environmental cues are transmitted to the interior of the cell via a complex network of signaling hubs. Receptor tyrosine kinases (RTKs) and trimeric G proteins are two such major signaling hubs in eukaryotes. Conventionally, canonical signal transduction via trimeric G proteins is thought to be triggered exclusively ...

    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.1420140112

    authors: Midde KK,Aznar N,Laederich MB,Ma GS,Kunkel MT,Newton AC,Ghosh P

    更新日期:2015-03-03 00:00:00

  • Expression of a Pim-1 transgene accelerates lymphoproliferation and inhibits apoptosis in lpr/lpr mice.

    abstract::Transgenic mice expressing the Pim-1 kinase are predisposed to develop T-cell lymphomas with a long latency period of about 7-9 months. However, the exact functional basis of the oncogenic activity of Pim-1 remains obscure. C57BL/6 mice homozygous for the lpr mutation develop a well-described lymphoproliferative syndr...

    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.90.22.10734

    authors: Möröy T,Grzeschiczek A,Petzold S,Hartmann KU

    更新日期:1993-11-15 00:00:00

  • Early tertiary elephant-shrews from Egypt and the origin of the Macroscelidea.

    abstract::Recent expeditions to the Fayum Depression, Egypt, have made possible the discovery of mandibles and a maxilla of a new genus and species of late Eocene elephant-shrew as well as initial evidence of the upper dentition of the early Oligocene taxon Metoldobotes. These fossils demonstrate that macroscelideans underwent ...

    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.88.21.9734

    authors: Simons EL,Holroyd PA,Bown TM

    更新日期:1991-11-01 00:00:00

  • Plant-derived anti-Lewis Y mAb exhibits biological activities for efficient immunotherapy against human cancer cells.

    abstract::Although current demands for therapeutic mAbs are growing quickly, production methods to date, including in vitro mammalian tissue culture and transgenic animals, provide only limited quantities at high cost. Several tumor-associated antigens in tumor cells have been identified as targets for therapeutic mAbs. Here 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.0603043103

    authors: Brodzik R,Glogowska M,Bandurska K,Okulicz M,Deka D,Ko K,van der Linden J,Leusen JH,Pogrebnyak N,Golovkin M,Steplewski Z,Koprowski H

    更新日期:2006-06-06 00:00:00

  • Molecular mechanism of water reorientational slowing down in concentrated ionic solutions.

    abstract::Water dynamics in concentrated ionic solutions plays an important role in a number of material and energy conversion processes such as the charge transfer at the electrolyte-electrode interface in aqueous rechargeable ion batteries. One long-standing puzzle is that all electrolytes, regardless of their "structure-maki...

    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.1707453114

    authors: Zhang Q,Wu T,Chen C,Mukamel S,Zhuang W

    更新日期:2017-09-19 00:00:00

  • Maturation of the olfactory sensory neurons by Apaf-1/caspase-9-mediated caspase activity.

    abstract::Although the apoptotic role of caspases has been largely understood, accumulating evidence in Drosophila suggests that caspases also control other processes than apoptotic cell death. However, how caspases contribute to the development of the mammalian nervous system remains obscure. Here, we provide unique evidence t...

    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.0910488107

    authors: Ohsawa S,Hamada S,Kuida K,Yoshida H,Igaki T,Miura M

    更新日期:2010-07-27 00:00:00

  • Energetics of the exchangeable quinone, QB, in Photosystem II.

    abstract::Photosystem II (PSII), the light-driven water/plastoquinone photooxidoreductase, is of central importance in the planetary energy cycle. The product of the reaction, plastohydroquinone (PQH2), is released into the membrane from the QB site, where it is formed. A plastoquinone (PQ) from the membrane pool then binds int...

    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.1910675116

    authors: De Causmaecker S,Douglass JS,Fantuzzi A,Nitschke W,Rutherford AW

    更新日期:2019-09-24 00:00:00

  • Properties of a mutant recA-encoded protein reveal a possible role for Escherichia coli recF-encoded protein in genetic recombination.

    abstract::A mutation partially suppressing the UV sensitivity caused by recF143 in a uvrA6 background was located at codon 37 of recA where GTG (valine) became ATG (methionine). This mutation, originally named srf-803, was renamed recA803. Little if any suppression of the recF143 defect in UV induction of a lexA regulon promote...

    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.85.18.6592

    authors: Madiraju MV,Templin A,Clark AJ

    更新日期:1988-09-01 00:00:00

  • Extension of the thermodynamics of small systems to open metastable states: an example.

    abstract::By using a simplified model of small open liquid-like clusters with surface effects, in the gas phase, it is shown how the statistical thermodynamics of small systems can be extended to include metastable supersaturated gaseous states not too far from the gas-liquid equilibrium transition point. To accomplish this, 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.95.22.12779

    authors: Hill TL,Chamberlin RV

    更新日期:1998-10-27 00:00:00