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 Repjournal_title
Scientific reportsauthors
Ono F,Chiba S,Isaka Y,Matsumoto S,Ma B,Katayama R,Araki M,Okuno Ydoi
10.1038/s41598-020-58877-9subject
Has Abstractpub_date
2020-02-07 00:00:00pages
2161issue
1issn
2045-2322pii
10.1038/s41598-020-58877-9journal_volume
10pub_type
杂志文章abstract::Biomarkers suitable for early diagnosis and monitoring disease progression are the cornerstone of developing disease-modifying treatments for neurodegenerative diseases such as Parkinson's disease (PD). Besides motor complications, PD is also characterized by deficits in visual processing. Here, we investigate how vir...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-68808-3
更新日期:2020-07-17 00:00:00
abstract::Volumetric and morphometric studies have demonstrated structural abnormalities related to chronic epilepsies on a cohort- and population-based level. On a single-patient level, specific patterns of atrophy or cortical reorganization may be widespread and heterogeneous but represent potential targets for further person...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-10707-1
更新日期:2017-09-07 00:00:00
abstract::Some studies have demonstrated interactions of AD-risk single nucleotide polymorphisms (SNPs) in non-APOE regions with APOE genotype. Nevertheless, no study reported interactions of expression quantitative trait locus (eQTL) for APOE with APOE genotype. In present study, we included 9286 unrelated AD patients and 8479...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-26398-1
更新日期:2018-05-23 00:00:00
abstract::We present a study of precessional magnetization switching in orthogonal spin-torque spin-valve devices at low temperatures. The samples consist of a spin-polarizing layer that is magnetized out-of-the film plane and an in-plane magnetized free and reference magnetic layer separated by non-magnetic metallic layers. We...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-37204-3
更新日期:2019-01-28 00:00:00
abstract::The intermolt crustacean Y-organ (YO) maintains a basal state mediated by pulsatile release of molt inhibiting hormone (MIH), a neuropeptide produced in the eyestalk ganglia, inhibiting YO ecdysteroidogenesis. Reduction of MIH results in YO activation and the animal enters premolt. In the crab, Gecarcinus lateralis, m...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-25368-x
更新日期:2018-05-09 00:00:00
abstract::This research aimed to explore the potential and mechanism of heat modified sawdust combined with Festuca arundinacea for the remediation of Pb-contaminated soil. We determined Pb concentration and biochemical indices in plants and soils, analyzed microbial communities in soil, and studied Pb distribution in subcellul...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-61668-x
更新日期:2020-03-13 00:00:00
abstract::Agrostemma githago L. (corn cockle) is an herbaceous plant mainly growing in Europe. The seeds of the corn cockle are toxic and poisonings were widespread in the past by consuming contaminated flour. The toxic principle of Agrostemma seeds was attributed to triterpenoid secondary metabolites. Indeed, this is in part t...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-72282-2
更新日期:2020-09-21 00:00:00
abstract::Using species distribution models and information on genetic structure and within-population variance observed in a series of common garden trials, we reconstructed a historical biogeography of trembling aspen in North America. We used an ensemble classifier modelling approach (RandomForest) to reconstruct palaeoclima...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-04871-7
更新日期:2017-07-05 00:00:00
abstract::Giant optical transmittance changes of over 300% in wide wavelength range from 500 nm to 2500 nm were observed in LaBaCo2O5.5+δ thin films annealed in air and ethanol ambient, respectively. The reduction process induces high density of ordered oxygen vacancies and the formation of LaBaCo2O5.5 (δ = 0) structure evidenc...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep37496
更新日期:2016-11-23 00:00:00
abstract::Exploration of genetic variant-to-gene relationships by quantitative trait loci such as expression QTLs is a frequently used tool in genome-wide association studies. However, the wide range of public QTL databases and the lack of batch annotation features complicate a comprehensive annotation of GWAS results. In this ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-75770-7
更新日期:2020-11-24 00:00:00
abstract::Understanding mechanisms mediating tumor metastasis is crucial for diagnostic and therapeutic targeting. Here, we take advantage of a transparent embryonic zebrafish xenograft model (eZXM) to visualize and track metastatic cells in real time using selective plane illumination microscopy (SPIM) for up to 30 h. Injected...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-69956-2
更新日期:2020-08-06 00:00:00
abstract::Changes in litterfall dynamics and soil properties due to anthropogenic or natural perturbations have important implications to soil carbon (C) and nutrient cycling via microbial pathway. Here we determine soil microbial responses to contrasting types of litter inputs (leaf vs. fine woody litter) and nitrogen (N) depo...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep19536
更新日期:2016-01-14 00:00:00
abstract::Bt cotton was genetically modified to produce insecticidal proteins targeting Lepidopteran pests and is therefore only minimally affected by caterpillar damage. This could lead to reduced levels of inherent, systemically inducible defensive compounds in Bt cotton which might benefit other important cotton herbivores s...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-38917-9
更新日期:2019-02-25 00:00:00
abstract::Pediococcus pentosaceus LBM 18 has shown potential as producer of an antibacterial and antifungal bacteriocin-like inhibitory substance (BLIS). BLIS inhibited the growth of spoilage bacteria belonging to Lactobacillus, Enterococcus and Listeria genera with higher activity than Nisaplin used as control. It gave rise to...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-68922-2
更新日期:2020-07-23 00:00:00
abstract::Tissue microarray (TMA) core images are a treasure trove for artificial intelligence applications. However, a common problem of TMAs is multiple sectioning, which can change the content of the intended tissue core and requires re-labelling. Here, we investigate different ensemble methods for colorectal tissue classifi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-021-81352-y
更新日期:2021-01-27 00:00:00
abstract::Periconceptional supplementation with folic acid reduces the occurrence of neural tube defects (NTDs). The association between maternal abnormalities in homocysteine metabolism (e.g., hyperhomocysteinaemia, folate deficiency and low vitamin B12) and the risk of NTDs-affected pregnancies has been widely evaluated in re...
journal_title:Scientific reports
pub_type: 杂志文章,meta分析
doi:10.1038/srep08510
更新日期:2015-03-02 00:00:00
abstract::A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-018-27850-y
更新日期:2018-06-22 00:00:00
abstract::Spiders can cause trophic cascades affecting litter decomposition rates. However, it remains unclear how spiders with different foraging strategies influence faunal communities, or present cascading effects on decomposition. Furthermore, increased dry periods predicted in future climates will likely have important con...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep12396
更新日期:2015-07-23 00:00:00
abstract::Widespread economic growth in China has led to increasing episodes of severe air pollution, especially in major urban areas. Thermal power plants represent a particularly important class of emissions. Here we present an evaluation of the predicted effectiveness of a series of recently proposed thermal power plant emis...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-19481-0
更新日期:2018-01-17 00:00:00
abstract::Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase domain containing 1 (NAPRT1) are the main human NAD salvage enzymes. NAD regulates energy metabolism and cell signaling, and the enzymes that control NAD availability are linked to pathologies such as cancer and neurodegeneration. ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep06311
更新日期:2014-09-09 00:00:00
abstract::Traditional strengthening ways, such as strain, precipitation, and solid-solution, come into effect by pinning the motion of dislocation. Here, through first-principles calculations we report on an extra-electron induced covalent strengthening mechanism, which alters chemical bonding upon the introduction of extra-val...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep00718
更新日期:2012-01-01 00:00:00
abstract::ING2 (inhibitor of growth family member 2) is a component of a chromatin-regulatory complex that represses gene expression and is implicated in cellular processes that promote tumor suppression. However, few direct genomic targets of ING2 have been identified and the mechanism(s) by which ING2 selectively regulates ge...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep02137
更新日期:2013-01-01 00:00:00
abstract::Successful tick feeding is facilitated by an assortment of pharmacologically-active factors in tick saliva that create an immunologically privileged micro-environment in the host's skin. Through a process known as saliva-assisted transmission, bioactive tick salivary factors modulate the host environment, promoting tr...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-49572-5
更新日期:2019-09-11 00:00:00
abstract::Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) that may lead to liver cirrhosis or hepatocellular carcinoma. Here, we examined the diagnostic utility of tri-antennary tri-sialylated mono-fucosylated glycan of alpha-1 antitrypsin (AAT-A3F), a non-invasive glycobi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-56947-1
更新日期:2020-01-15 00:00:00
abstract::Clouds play a major role in the climate system, but large uncertainties remain about their decadal variations. Here we report a widespread decrease in cloud cover since the 1970 s over the Mediterranean region, in particular during the 1970 s-1980 s, especially in the central and eastern areas and during springtime. C...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep41475
更新日期:2017-02-02 00:00:00
abstract::Alzheimer's disease (AD), an irreversible progressive neurodegenerative disease, causes characteristic cognitive impairment, and no curative treatments are currently available. Stem cell transplantation offers a powerful tool for the treatment of AD. We conducted a systematic review and meta-analysis of data from cont...
journal_title:Scientific reports
pub_type: 杂志文章,meta分析,评审
doi:10.1038/srep12134
更新日期:2015-07-10 00:00:00
abstract::Synchrotron radiation microtomography (SRμCT) is a nominally non-destructive 3D imaging technique which can visualise the internal structures of whole soft tissues. As a multi-stage technique, the cumulative benefits of optimising sample preparation, scanning parameters and signal processing can improve SRμCT imaging ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-30520-8
更新日期:2018-08-13 00:00:00
abstract::We introduce a simple criterion to identify two-dimensional (2D) materials based on the comparison between experimental lattice constants and lattice constants mainly obtained from Materials-Project (MP) density functional theory (DFT) calculation repository. Specifically, if the relative difference between the two la...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-05402-0
更新日期:2017-07-12 00:00:00
abstract::Objectives were to evaluate the role of canonical WNT signaling in development of the preimplantation embryo. Signaling was activated with 2-Amino-4-(3,4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine (AMBMP) and inhibited with Dickkopf-related protein 1 (DKK1). Treatment of bovine embryos with AMBMP at da...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep01266
更新日期:2013-01-01 00:00:00
abstract::All-spin logic device (ASLD) has attracted increasing interests as one of the most promising post-CMOS device candidates, thanks to its low power, non-volatility and logic-in-memory structure. Here we investigate the key current-limiting factors and develop a physics-based model of ASLD through nano-magnet switching, ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep14905
更新日期:2015-10-09 00:00:00