当前位置： SCI文献检索 > Scientific Reports期刊下所有文献 > Improvement in predicting drug sensitivity changes associated with protein mutations using a molecular dynamics based alchemical mutation method.

Improvement in predicting drug sensitivity changes associated with protein mutations using a molecular dynamics based alchemical mutation method.

Abstract：

:While molecular-targeted drugs have demonstrated strong therapeutic efficacy against diverse diseases such as cancer and infection, the appearance of drug resistance associated with genetic variations in individual patients or pathogens has severely limited their clinical efficacy. Therefore, precision medicine approaches based on the personal genomic background provide promising strategies to enhance the effectiveness of molecular-targeted therapies. However, identifying drug resistance mutations in individuals by combining DNA sequencing and in vitro analyses is generally time consuming and costly. In contrast, in silico computation of protein-drug binding free energies allows for the rapid prediction of drug sensitivity changes associated with specific genetic mutations. Although conventional alchemical free energy computation methods have been used to quantify mutation-induced drug sensitivity changes in some protein targets, these methods are often adversely affected by free energy convergence. In this paper, we demonstrate significant improvements in prediction performance and free energy convergence by employing an alchemical mutation protocol, MutationFEP, which directly estimates binding free energy differences associated with protein mutations in three types of a protein and drug system. The superior performance of MutationFEP appears to be attributable to its more-moderate perturbation scheme. Therefore, this study provides a deeper level of insight into computer-assisted precision medicine.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Ono F,Chiba S,Isaka Y,Matsumoto S,Ma B,Katayama R,Araki M,Okuno Y

doi

10.1038/s41598-020-58877-9

subject

Has Abstract

pub_date

2020-02-07 00:00:00

pages

2161

issue

1

issn

2045-2322

pii

10.1038/s41598-020-58877-9

journal_volume

10

pub_type

杂志文章

相关文献

Scientific Reports文献大全
  • Fragmented mitochondrial genomes in two suborders of parasitic lice of eutherian mammals (Anoplura and Rhynchophthirina, Insecta).

    abstract：:Parasitic lice (order Phthiraptera) infest birds and mammals. The typical animal mitochondrial (mt) genome organization, which consists of a single chromosome with 37 genes, was found in chewing lice in the suborders Amblycera and Ischnocera. The sucking lice (suborder Anoplura) known, however, have fragmented mt geno...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/srep17389

    authors： Shao R,Barker SC,Li H,Song S,Poudel S,Su Y

    更新日期：2015-11-30 00:00:00

  • Controlled mud-crack patterning and self-organized cracking of polydimethylsiloxane elastomer surfaces.

    abstract：:Exploiting pattern formation - such as that observed in nature - in the context of micro/nanotechnology could have great benefits if coupled with the traditional top-down lithographic approach. Here, we demonstrate an original and simple method to produce unique, localized and controllable self-organised patterns on e...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/srep14787

    authors： Seghir R,Arscott S

    更新日期：2015-10-06 00:00:00

  • Changing fluxes of carbon and other solutes from the Mekong River.

    abstract：:Rivers are an important aquatic conduit that connects terrestrial sources of dissolved inorganic carbon (DIC) and other elements with oceanic reservoirs. The Mekong River, one of the world's largest rivers, is firstly examined to explore inter-annual fluxes of dissolved and particulate constituents during 1923-2011 an...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/srep16005

    authors： Li S,Bush RT

    更新日期：2015-11-02 00:00:00

  • Video-rate volumetric neuronal imaging using 3D targeted illumination.

    abstract：:Fast volumetric microscopy is required to monitor large-scale neural ensembles with high spatio-temporal resolution. Widefield fluorescence microscopy can image large 2D fields of view at high resolution and speed while remaining simple and costeffective. A focal sweep add-on can further extend the capacity of widefie...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/s41598-018-26240-8

    authors： Xiao S,Tseng HA,Gritton H,Han X,Mertz J

    更新日期：2018-05-21 00:00:00

  • Multiple uprising invasions of Pelophylax water frogs, potentially inducing a new hybridogenetic complex.

    abstract：:The genetic era has revolutionized our perception of biological invasions. Yet, it is usually too late to understand their genesis for efficient management. Here, we take the rare opportunity to reconstruct the scenario of an uprising invasion of the famous water frogs (Pelophylax) in southern France, through a fine-s...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/s41598-017-06655-5

    authors： Dufresnes C,Denoël M,di Santo L,Dubey S

    更新日期：2017-07-26 00:00:00

  • The shallow structure of Solfatara Volcano, Italy, revealed by dense, wide-aperture seismic profiling.

    abstract：:Two active-source, high-resolution seismic profiles were acquired in the Solfatara tuff cone in May and November 2014, with dense, wide-aperture arrays. Common Receiver Surface processing was crucial in improving signal-to-noise ratio and reflector continuity. These surveys provide, for the first time, high-resolution...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/s41598-017-17589-3

    authors： Bruno PPG,Maraio S,Festa G

    更新日期：2017-12-12 00:00:00

  • Direct nitrogen fixation at the edges of graphene nanoplatelets as efficient electrocatalysts for energy conversion.

    abstract：:Nitrogen fixation is essential for the synthesis of many important chemicals (e.g., fertilizers, explosives) and basic building blocks for all forms of life (e.g., nucleotides for DNA and RNA, amino acids for proteins). However, direct nitrogen fixation is challenging as nitrogen (N₂) does not easily react with other ...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/srep02260

    authors： Jeon IY,Choi HJ,Ju MJ,Choi IT,Lim K,Ko J,Kim HK,Kim JC,Lee JJ,Shin D,Jung SM,Seo JM,Kim MJ,Park N,Dai L,Baek JB

    更新日期：2013-01-01 00:00:00

  • Novel codon-optimized mini-intronic plasmid for efficient, inexpensive, and xeno-free induction of pluripotency.

    abstract：:The development of human induced pluripotent stem cell (iPSC) technology has revolutionized the regenerative medicine field. This technology provides a powerful tool for disease modeling and drug screening approaches. To circumvent the risk of random integration into the host genome caused by retroviruses, non-integra...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/srep08081

    authors： Diecke S,Lu J,Lee J,Termglinchan V,Kooreman NG,Burridge PW,Ebert AD,Churko JM,Sharma A,Kay MA,Wu JC

    更新日期：2015-01-28 00:00:00

  • RSH enzyme diversity for (p)ppGpp metabolism in Phaeodactylum tricornutum and other diatoms.

    abstract：:The nucleotides guanosine tetraphosphate and pentaphosphate (together known as (p)ppGpp or magic spot) are produced in plant plastids from GDP/GTP and ATP by RelA-SpoT homologue (RSH) enzymes. In the model plant Arabidopsis (p)ppGpp regulates chloroplast transcription and translation to affect growth, and is also impl...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/s41598-019-54207-w

    authors： Avilan L,Puppo C,Villain A,Bouveret E,Menand B,Field B,Gontero B

    更新日期：2019-11-27 00:00:00

  • Somatic Copy Number Alterations at Oncogenic Loci Show Diverse Correlations with Gene Expression.

    abstract：:Somatic copy number alterations (SCNAs) affecting oncogenic drivers have a firmly established role in promoting cancer. However, no agreed-upon standard exists for calling locus-specific amplifications and deletions in each patient sample. Here, we report the correlative analysis of copy number amplitude and length wi...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/srep19649

    authors： Roszik J,Wu CJ,Siroy AE,Lazar AJ,Davies MA,Woodman SE,Kwong LN

    更新日期：2016-01-20 00:00:00

  • The Mutation of Glu at Amino Acid 3838 of AtMDN1 Provokes Pleiotropic Developmental Phenotypes in Arabidopsis.

    abstract：:MDN1/Rea1, as an AAA-type ATPase, is predicted to be the largest protein involved in pre-ribosome maturation in most organisms. However, its function in plant growth and development is poorly understood. Here, we characterized a novel Arabidopsis mutant, dwarf &short root (dsr) 1, which shows pleiotropic developmental...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/srep36446

    authors： Li PC,Yu SW,Li K,Huang JG,Wang XJ,Zheng CC

    更新日期：2016-11-08 00:00:00

  • Dimerization in tailoring uptake efficacy of the HSV-1 derived membranotropic peptide gH625.

    abstract：:gH625 constitutes a promising delivery vehicle for the transport of therapeutic biomacromolecules across membrane barriers. We report an application of multivalency to create a complex nanosystem for delivery and to elucidate the mechanism of peptide-lipid bilayer interactions. Multivalency may offer a route to enhanc...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/s41598-017-09001-x

    authors： Falanga A,Valiante S,Galdiero E,Franci G,Scudiero O,Morelli G,Galdiero S

    更新日期：2017-08-25 00:00:00

  • An integrated platform for genome engineering and gene expression perturbation in Plasmodium falciparum.

    abstract：:Establishing robust genome engineering methods in the malarial parasite, Plasmodium falciparum, has the potential to substantially improve the efficiency with which we gain understanding of this pathogen's biology to propel treatment and elimination efforts. Methods for manipulating gene expression and engineering the...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/s41598-020-77644-4

    authors： Nasamu AS,Falla A,Pasaje CFA,Wall BA,Wagner JC,Ganesan SM,Goldfless SJ,Niles JC

    更新日期：2021-01-11 00:00:00

  • Author Correction: Artificial Intelligence and Machine learning based prediction of resistant and susceptible mutations in Mycobacterium tuberculosis.

    abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title：Scientific reports

    pub_type： 已发布勘误

    doi：10.1038/s41598-020-71840-y

    authors： Jamal S,Khubaib M,Gangwar R,Grover S,Grover A,Hasnain SE

    更新日期：2020-09-01 00:00:00

  • Maternal-placental-fetal biodistribution of multimodal polymeric nanoparticles in a pregnant rat model in mid and late gestation.

    abstract：:Multimodal polymeric nanoparticles have many exciting diagnostic and therapeutic applications, yet their uptake and passage by the placenta, and applications in the treatment of pregnancy complications have not been thoroughly investigated. In this work, the maternal-fetal-placental biodistribution of anionic and cati...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/s41598-017-03128-7

    authors： Ho D,Leong JW,Crew RC,Norret M,House MJ,Mark PJ,Waddell BJ,Iyer KS,Keelan JA

    更新日期：2017-06-06 00:00:00

  • Association between sea lice (Lepeophtheirus salmonis) infestation on Atlantic salmon farms and wild Pacific salmon in Muchalat Inlet, Canada.

    abstract：:Growth in salmon aquaculture over the past two decades has raised concerns regarding the potential impacts of the industry on neighboring ecosystems and wild fish productivity. Despite limited evidence, sea lice have been identified as a major cause for the decline in some wild Pacific salmon populations on the west c...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/s41598-018-22458-8

    authors： Nekouei O,Vanderstichel R,Thakur K,Arriagada G,Patanasatienkul T,Whittaker P,Milligan B,Stewardson L,Revie CW

    更新日期：2018-03-05 00:00:00

  • GSTP1 and GSTO1 single nucleotide polymorphisms and the response of bladder cancer patients to intravesical chemotherapy.

    abstract：:SNPs may restrict cell detoxification activity and be a potential risk factor for cancer chemosensitivity. We evaluated the predictive value of these polymorphisms on the sensitivity of bladder cancer patients to epirubicin and mitomycin chemotherapy instillation as well as their toxicities. SNPs were analyzed by TaqM...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/srep14000

    authors： Deng X,Yang X,Cheng Y,Liu X,Li X,Zhao R,Qin C,Lu Q,Yin C

    更新日期：2015-09-10 00:00:00

  • Mapping species richness using opportunistic samples: a case study on ground-floor bryophyte species richness in the Belgian province of Limburg.

    abstract：:In species richness studies, citizen-science surveys where participants make individual decisions regarding sampling strategies provide a cost-effective approach to collect a large amount of data. However, it is unclear to what extent the bias inherent to opportunistically collected samples may invalidate our inferenc...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/s41598-019-55593-x

    authors： Neyens T,Diggle PJ,Faes C,Beenaerts N,Artois T,Giorgi E

    更新日期：2019-12-13 00:00:00

  • Assessing the benefits of early pandemic influenza vaccine availability: a case study for Ontario, Canada.

    abstract：:New vaccine production technologies can significantly shorten the timelines for availability of a strain-specific vaccine in the event of an influenza pandemic. We sought to evaluate the potential benefits of early vaccination in reducing the clinical attack rate (CAR), taking into account the timing and speed of vacc...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/s41598-018-24764-7

    authors： Champredon D,Laskowski M,Charland N,Moghadas SM

    更新日期：2018-04-24 00:00:00

  • The network organization of protein interactions in the spliceosome is reproduced by the simple rules of food-web models.

    abstract：:The network structure of biological systems provides information on the underlying processes shaping their organization and dynamics. Here we examined the structure of the network depicting protein interactions within the spliceosome, the macromolecular complex responsible for splicing in eukaryotic cells. We show the...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/srep14865

    authors： Pires MM,Cantor M,Guimarães PR,de Aguiar MA,Dos Reis SF,Coltri PP

    更新日期：2015-10-07 00:00:00

  • Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation.

    abstract：:In Duchenne muscular dystrophy, progressive loss of muscle tissue is accompanied by fibrosis, chronic inflammation and reduced muscle regenerative capacity. Although much is known about the development of fibrosis and chronic inflammation in muscular dystrophy, less is known about how they are mechanistically linked t...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/srep24708

    authors： Arecco N,Clarke CJ,Jones FK,Simpson DM,Mason D,Beynon RJ,Pisconti A

    更新日期：2016-05-31 00:00:00

  • Altered RNA editing in 3' UTR perturbs microRNA-mediated regulation of oncogenes and tumor-suppressors.

    abstract：:RNA editing is a molecular event that alters specific nucleotides in RNA post-transcriptionally. RNA editing has the potential to impact a variety of cellular processes and is implicated in diseases such as cancer. Yet, the precise mechanisms by which RNA editing controls cellular processes are poorly understood. Here...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/srep23226

    authors： Zhang L,Yang CS,Varelas X,Monti S

    更新日期：2016-03-16 00:00:00

  • Time of Day and its Association with Risk of Death and Chance of Discharge in Critically Ill Patients: A Retrospective Study.

    abstract：:Outcomes following admission to intensive care units (ICU) may vary with time and day. This study investigated associations between time of day and risk of ICU mortality and chance of ICU discharge in acute ICU admissions. Adult patients (age ≥ 18 years) who were admitted to ICUs participating in the Austrian intensiv...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/s41598-019-48947-y

    authors： Zajic P,Bauer P,Rhodes A,Moreno R,Fellinger T,Metnitz B,Posch M,Metnitz PGH

    更新日期：2019-08-29 00:00:00

  • Novel identified associations of RGS1 and RASGRP1 variants in IgA Nephropathy.

    abstract：:Known susceptibility loci together can only explain about 6-8% of the disease heritability of IgA nephropathy (IgAN), suggesting that there are still a large number of genetic variants remained to be discovered. We previously identified IgAN and systemic lupus erythematosus (SLE)/lupus nephritis (LN) shared many loci ...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/srep35781

    authors： Zhou XJ,Nath SK,Qi YY,Sun C,Hou P,Zhang YM,Lv JC,Shi SF,Liu LJ,Chen R,Yang W,He KZ,Li Y,Zhang H

    更新日期：2016-11-02 00:00:00

  • Imitation in Angelman syndrome: the role of social engagement.

    abstract：:Individuals with Angelman syndrome (AS) are characterized by severe cognitive impairments alongside an enhanced drive for social engagement. As knowledge on imitation skills in this population is limited, we conducted the first controlled study of imitation in AS. We examined how 23 individuals with AS and 21 typicall...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/s41598-020-72079-3

    authors： Micheletti S,Vivanti G,Renzetti S,Martelli P,Calza S,“Imitation in Angelman” Study Group.,Fazzi E

    更新日期：2020-10-02 00:00:00

  • Metabolomic identification of biochemical changes induced by fluoxetine and imipramine in a chronic mild stress mouse model of depression.

    abstract：:Metabolomics was applied to a C57BL/6N mouse model of chronic unpredictable mild stress (CMS). Such mice were treated with two antidepressants from different categories: fluoxetine and imipramine. Metabolic profiling of the hippocampus was performed using gas chromatography-mass spectrometry analysis on samples prepar...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/srep08890

    authors： Zhao J,Jung YH,Jang CG,Chun KH,Kwon SW,Lee J

    更新日期：2015-03-09 00:00:00

  • Effects of a microbial restoration substrate on plant growth and rhizosphere bacterial community in a continuous tomato cropping greenhouse.

    abstract：:Continuous cropping of tomato is increasingly practiced in greenhouse cultivation, leading to several soil-related obstacles. In this study, a type of microbial restoration substrate (MRS) was used to amend soils from the re-cropping of tomato for 8 years under greenhouse-cultivated conditions. Two treatments were est...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/s41598-020-70737-0

    authors： Zheng X,Wang Z,Zhu Y,Wang J,Liu B

    更新日期：2020-08-13 00:00:00

  • Time course of bilateral microglial activation in a mouse model of laser-induced glaucoma.

    abstract：:Microglial activation is associated with glaucoma. In the model of unilateral laser-induced ocular hypertension (OHT), the time point at which the inflammatory process peaks remains unknown. Different time points (1, 3, 5, 8, and 15 d) were compared to analyze signs of microglial activation both in OHT and contralater...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/s41598-020-61848-9

    authors： Ramírez AI,de Hoz R,Fernández-Albarral JA,Salobrar-Garcia E,Rojas B,Valiente-Soriano FJ,Avilés-Trigueros M,Villegas-Pérez MP,Vidal-Sanz M,Triviño A,Ramírez JM,Salazar JJ

    更新日期：2020-03-17 00:00:00

  • Electrophysiological evidence of inhibited orthographic regularity effect on the recognition of real Chinese characters.

    abstract：:Orthographic regularity is important for processing Chinese characters. However, the issues how orthographic regularity influences the visual recognition of real Chinese characters and whether common processes related to the potential effect exist between successive (SUCC) and concurrent (CONC) conditions with asynchr...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/srep23275

    authors： He W,Fan C,Ren J,Liu T,Zhang M,Luo W

    更新日期：2016-03-23 00:00:00

  • Lighting up ultraviolet fluorescence from chicken albumen through plasmon resonance energy transfer of gold nanoparticles.

    abstract：:Au nanoparticles (AuNPs), which easily aggregate in organic thin film, are observed to well-disperse in chicken albumen thin films. The incorporated AuNPs is distributed uniformly inside the thin film and is as dense as 650 (particles/μm(3)). In addition, enhanced ultraviolet (UV) fluorescence centered at 350 nm is ob...

    journal_title：Scientific reports

    pub_type： 杂志文章

    doi：10.1038/srep01505

    authors： Tsung Chen I,Chang PH,Chang YC,Guo TF

    更新日期：2013-01-01 00:00:00