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


: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.


Sci Rep


Scientific reports


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




Has Abstract


2020-02-07 00:00:00












  • Pu isotopes in soils collected downwind from Lop Nor: regional fallout vs. global fallout.

    abstract::For the first time, soil core samples from the Jiuquan region have been analyzed for Pu isotopes for radioactive source identification and radiological assessment. The Jiuquan region is in downwind from the Lop Nor Chinese nuclear test (CNT) site. The high Pu inventories (13 to 546 Bq/m(2)) in most of the sampling loc...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Bu W,Ni Y,Guo Q,Zheng J,Uchida S

    更新日期:2015-07-17 00:00:00

  • Changes in micro-relief during different water erosive stages of purple soil under simulated rainfall.

    abstract::This study investigated the variation characteristics of micro-topography during successive erosive stages of water erosion: splash erosion (SpE), sheet erosion (ShE), and rill erosion (RE). Micro-topography was quantified using surface elevation change, soil roughness (SR) and multifractal model. Results showed that ...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Luo J,Zheng Z,Li T,He S

    更新日期:2018-02-22 00:00:00

  • Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model.

    abstract::The number of osteoarthritis patients is increasing with the rise in the number of elderly people in developed countries. Osteoarthritis, which causes joint pain and deformity leading to loss of activities of daily living, is often treated surgically. Here we show that mechanical stress promotes accumulation of reacti...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Kaneko Y,Tanigawa N,Sato Y,Kobayashi T,Nakamura S,Ito E,Soma T,Miyamoto K,Kobayashi S,Harato K,Matsumoto M,Nakamura M,Niki Y,Miyamoto T

    更新日期:2019-12-10 00:00:00

  • Toxic metabolites, MAPK and Nrf2/Keap1 signaling pathways involved in oxidative toxicity in mice liver after chronic exposure to Mequindox.

    abstract::Mequindox (MEQ) is a synthetic antimicrobial agent of quinoxaline-1,4-dioxide group (QdNOs). The liver is regarded as the toxicity target of QdNOs, and the role of N → O group-associated various toxicities mediated by QdNOs is well recognized. However, the mechanism underlying the in vivo effects of MEQ on the liver, ...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Liu Q,Lei Z,Huang A,Wu Q,Xie S,Awais I,Dai M,Wang X,Yuan Z

    更新日期:2017-02-03 00:00:00

  • A Flexible Electret Membrane with Persistent Electrostatic Effect and Resistance to Harsh Environment for Energy Harvesting.

    abstract::A novel flexible electret membrane, exhibiting persistent electrostatic effect, distinctive temperature stability and outstanding capability of resistance to harsh environment and fatigue, is demonstrated by experiment. Its excellent electret performance is correlated to the synergy of three factors, which are space c...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Huiming X,Gangjin C,Xumin C,Zhi C

    更新日期:2017-08-16 00:00:00

  • Multi-omics characterization of a diet-induced obese model of non-alcoholic steatohepatitis.

    abstract::To improve the understanding of the complex biological processes underlying the development of non-alcoholic steatohepatitis (NASH), a multi-omics approach combining bulk RNA-sequencing based transcriptomics, quantitative proteomics and single-cell RNA-sequencing was used to characterize tissue biopsies from histologi...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Ægidius HM,Veidal SS,Feigh M,Hallenborg P,Puglia M,Pers TH,Vrang N,Jelsing J,Kornum BR,Blagoev B,Rigbolt KTG

    更新日期:2020-01-24 00:00:00

  • Self-healing capacity of nuclear glass observed by NMR spectroscopy.

    abstract::Safe management of high level nuclear waste is a worldwide significant issue for which vitrification has been selected by many countries. There exists a crucial need for improving our understanding of the ageing of the glass under irradiation. While external irradiation by ions provides a rapid simulation of damage in...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Charpentier T,Martel L,Mir AH,Somers J,Jégou C,Peuget S

    更新日期:2016-05-05 00:00:00

  • Quantifying replicative senescence as a tumor suppressor pathway and a target for cancer therapy.

    abstract::To study quantitatively replicative senescence as a tumor suppressor mechanism, we investigate the distribution of a growing clonal cell population restricted by Hayflick's limit. We find that in the biologically relevant range of parameters, if the imbalance between cell division and death is moderate or low (high de...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Rodriguez-Brenes IA,Wodarz D,Komarova NL

    更新日期:2015-12-09 00:00:00

  • Network science applied to forest megaplots: tropical tree species coexist in small-world networks.

    abstract::Network analysis is an important tool to analyze the structure of complex systems such as tropical forests. Here, we infer spatial proximity networks in tropical forests by using network science. First, we focus on tree neighborhoods to derive spatial tree networks from forest inventory data. In a second step, we cons...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Schmid JS,Taubert F,Wiegand T,Sun IF,Huth A

    更新日期:2020-08-06 00:00:00

  • Species-specific antifungal activity of blue light.

    abstract::Fungal pathogens represent a significant threat to immunocompromised patients or individuals with traumatic injury. Strategies to efficiently remove fungal spores from hospital surfaces and, ideally, patient skin thus offer the prospect of dramatically reducing infections in at-risk patients. Photodynamic inactivation...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Trzaska WJ,Wrigley HE,Thwaite JE,May RC

    更新日期:2017-07-04 00:00:00

  • The response of an egg parasitoid to substrate-borne semiochemicals is affected by previous experience.

    abstract::Animals can adjust their behaviour according to previous experience gained during foraging. In parasitoids, experience plays a key role in host location, a hierarchical process in which air-borne and substrate-borne semiochemicals are used to find hosts. In nature, chemical traces deposited by herbivore hosts when wal...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Peri E,Salerno G,Slimani T,Frati F,Conti E,Colazza S,Cusumano A

    更新日期:2016-06-02 00:00:00

  • Bridging the connection between effective viscosity and electrical conductivity through water content in the upper mantle.

    abstract::Upper mantle viscosity plays a key role in understanding plate tectonics and is usually extrapolated from laboratory-based creep measurements of upper mantle conditions or constrained by modeling geodetic and post-seismic observations. At present, an effective method to obtain a high-resolution viscosity structure is ...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Xu Y,Zhang A,Yang B,Bao X,Wang Q,Xia J,Yang W

    更新日期:2018-01-29 00:00:00

  • Near-Field Scanning Microwave Microscopy in the Single Photon Regime.

    abstract::The microwave properties of nano-scale structures are important in a wide variety of applications in quantum technology. Here we describe a low-power cryogenic near-field scanning microwave microscope (NSMM) which maintains nano-scale dielectric contrast down to the single microwave photon regime, up to 109 times lowe...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Geaney S,Cox D,Hönigl-Decrinis T,Shaikhaidarov R,Kubatkin SE,Lindström T,Danilov AV,de Graaf SE

    更新日期:2019-08-29 00:00:00

  • Migrating oligodendrocyte progenitor cells swell prior to soma dislocation.

    abstract::The migration of oligodendrocyte progenitor cells (OPCs) to the white matter is an indispensable requirement for an intact brain function. The mechanism of cell migration in general is not yet completely understood. Nevertheless, evidence is accumulating that besides the coordinated rearrangement of the cytoskeleton, ...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Happel P,Möller K,Schwering NK,Dietzel ID

    更新日期:2013-01-01 00:00:00

  • Computational design and characterization of nanobody-derived peptides that stabilize the active conformation of the β2-adrenergic receptor (β2-AR).

    abstract::This study aimed to design and functionally characterize peptide mimetics of the nanobody (Nb) related to the β2-adrenergic receptor (β2-AR) (nanobody-derived peptide, NDP). We postulated that the computationally derived and optimized complementarity-determining region 3 (CDR3) of Nb is sufficient for its interaction ...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Sencanski M,Glisic S,Šnajder M,Veljkovic N,Poklar Ulrih N,Mavri J,Vrecl M

    更新日期:2019-11-12 00:00:00

  • Nanocomposite Metamaterials Based on Self-assembled Titanium Dioxide Rolls with Embedded Gold Nanoparticles.

    abstract::An experimental method for fabrication of a nanocomposite metamaterial based on a self-assembly of titanium dioxide microtubes with encapsulated gold nanoparticles (NPs) is proposed. The formation of microtubes is induced by laser irradiation in the presence of an external magnetic field. It is shown that the variatio...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Kutrovskaya S,Kucherik A,Osipov A,Samyshkin V,Istratov A,Kavokin AV

    更新日期:2019-05-07 00:00:00

  • Metagenomic evidence of stronger effect of stylo (legume) than bahiagrass (grass) on taxonomic and functional profiles of the soil microbial community.

    abstract::Plants are key determinants of soil microbial community (SMC). Legumes and grasses are distinct groups in various ecosystems; however, how they differentially shape SMC structure and functioning has yet to be explored. Here, we investigate SMC in soils grown with stylo (legume) or bahiagrass (grass). Soil metagenomic ...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Zhou Y,Zhu H,Fu S,Yao Q

    更新日期:2017-08-31 00:00:00

  • Corrigendum: Treponema pallidum (syphilis) antigen TpF1 induces angiogenesis through the activation of the IL-8 pathway.

    abstract::This corrects the article DOI: 10.1038/srep18785. ...

    journal_title:Scientific reports

    pub_type: 已发布勘误


    authors: Pozzobon T,Facchinello N,Bossi F,Capitani N,Benagiano M,Di Benedetto G,Zennaro C,West N,Codolo G,Bernardini M,Baldari CT,D'Elios MM,Pellegrini L,Argenton F,de Bernard M

    更新日期:2018-02-16 00:00:00

  • Transcriptome Analysis in Spleen Reveals Differential Regulation of Response to Newcastle Disease Virus in Two Chicken Lines.

    abstract::Enhancing genetic resistance of chickens to Newcastle Disease Virus (NDV) provides a promising way to improve poultry health, and to alleviate poverty and food insecurity in developing countries. In this study, two inbred chicken lines with different responses to NDV, Fayoumi and Leghorn, were challenged with LaSota N...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Zhang J,Kaiser MG,Deist MS,Gallardo RA,Bunn DA,Kelly TR,Dekkers JCM,Zhou H,Lamont SJ

    更新日期:2018-01-19 00:00:00

  • The breeding strategy of female jumbo squid Dosidicus gigas: energy acquisition and allocation.

    abstract::Reproductive investment generally involves a trade-off between somatic growth and energy allocation for reproduction. Previous studies have inferred that jumbo squid Dosidicus gigas support growth during maturation through continuous feeding (an "income" source). However, our recent work suggests possible remobilizati...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Chen X,Han F,Zhu K,Punt AE,Lin D

    更新日期:2020-06-15 00:00:00

  • Horizontally-acquired genetic elements in the mitochondrial genome of a centrohelid Marophrys sp. SRT127.

    abstract::Mitochondrial genomes exhibit diverse features among eukaryotes in the aspect of gene content, genome structure, and the mobile genetic elements such as introns and plasmids. Although the number of published mitochondrial genomes is increasing at tremendous speed, those of several lineages remain unexplored. Here, we ...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Nishimura Y,Shiratori T,Ishida KI,Hashimoto T,Ohkuma M,Inagaki Y

    更新日期:2019-03-19 00:00:00

  • Enhanced electrocatalytic performance for oxygen reduction via active interfaces of layer-by-layered titanium nitride/titanium carbonitride structures.

    abstract::Cathode materials always limit the performance of fuel cells while the commercial platinum-based catalysts hardly meet the requirements of low cost, durable and stable. Here a non-precious metal oxygen reduction reaction (ORR) electocatalyst based on titanium nitride/titanium carbonitride hierarchical structures (TNTC...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Jin Z,Li P,Xiao D

    更新日期:2014-10-22 00:00:00

  • Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation.

    abstract::Neural connectivity requires neuronal differentiation, axon growth, and precise target innervation. Midbrain dopaminergic neurons project via the nigrostriatal pathway to the striatum to regulate voluntary movement. While the specification and differentiation of these neurons have been extensively studied, the molecul...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Hegarty SV,Wyatt SL,Howard L,Stappers E,Huylebroeck D,Sullivan AM,O'Keeffe GW

    更新日期:2017-08-17 00:00:00

  • Direct observation of melting in a two-dimensional driven granular system.

    abstract::Melting is considered to be one of the most fundamental problems in physical science. Generally, dimensionality plays an important role in melting. In three-dimension, it's well known that a crystal melts directly into a liquid via a first-order transition. In two-dimension (2D), however, the melting process has been ...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Sun X,Li Y,Ma Y,Zhang Z

    更新日期:2016-04-07 00:00:00

  • Comparative Transcriptional Profiling and Physiological Responses of Two Contrasting Oat Genotypes under Salt Stress.

    abstract::Salinity is one of the major abiotic factors that affect productivity in oat. Here, we report a comparison of the transcriptomes of two hexaploid oat cultivars, 'Hanyou-5' and 'Huazao-2', which differ with respect to salt tolerance, in seedlings exposed to salt stress. Analysis of the assembled unigenes from the osmot...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Wu B,Munkhtuya Y,Li J,Hu Y,Zhang Q,Zhang Z

    更新日期:2018-11-02 00:00:00

  • Methoxydiphenylamine-substituted fluorene derivatives as hole transporting materials: role of molecular interaction on device photovoltaic performance.

    abstract::The molecular structure of the hole transporting material (HTM) play an important role in hole extraction in a perovskite solar cells. It has a significant influence on the molecular planarity, energy level, and charge transport properties. Understanding the relationship between the chemical structure of the HTM's and...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Tiazkis R,Paek S,Daskeviciene M,Malinauskas T,Saliba M,Nekrasovas J,Jankauskas V,Ahmad S,Getautis V,Khaja Nazeeruddin M

    更新日期:2017-03-10 00:00:00

  • Entropic uncertainty relations for Markovian and non-Markovian processes under a structured bosonic reservoir.

    abstract::The uncertainty relation is a fundamental limit in quantum mechanics and is of great importance to quantum information processing as it relates to quantum precision measurement. Due to interactions with the surrounding environment, a quantum system will unavoidably suffer from decoherence. Here, we investigate the dyn...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Wang D,Huang AJ,Hoehn RD,Ming F,Sun WY,Shi JD,Ye L,Kais S

    更新日期:2017-04-21 00:00:00

  • Effect of radiochemotherapy on the cognitive function and diffusion tensor and perfusion weighted imaging for high-grade gliomas: A prospective study.

    abstract::This study aimed to explore the effects of radiochemotherapy on the neurocognitive function of patients with high-grade gliomas (HGG). The mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), event-related potential P300 (ERP-P300), and specific MRI parameters were compared, and the associations...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Bian Y,Meng L,Peng J,Li J,Wei R,Huo L,Yang H,Wang Y,Fu J,Shen L,Hong J

    更新日期:2019-04-12 00:00:00

  • Drought and child mortality: a meta-analysis of small-scale surveys from Ethiopia.

    abstract::Despite the intuitive connection between drought and mortality, we still lack a sound quantitative synthesis of evidence drawn from the available data. In this study, we estimate the pooled under-five death rates (U5DR) and assess the effect of drought on child death in Ethiopia. Small-scale mortality surveys were sea...

    journal_title:Scientific reports

    pub_type: 杂志文章,meta分析


    authors: Delbiso TD,Altare C,Rodriguez-Llanes JM,Doocy S,Guha-Sapir D

    更新日期:2017-05-19 00:00:00

  • Macromolecularly crowded in vitro microenvironments accelerate the production of extracellular matrix-rich supramolecular assemblies.

    abstract::Therapeutic strategies based on the principles of tissue engineering by self-assembly put forward the notion that functional regeneration can be achieved by utilising the inherent capacity of cells to create highly sophisticated supramolecular assemblies. However, in dilute ex vivo microenvironments, prolonged culture...

    journal_title:Scientific reports

    pub_type: 杂志文章


    authors: Kumar P,Satyam A,Fan X,Collin E,Rochev Y,Rodriguez BJ,Gorelov A,Dillon S,Joshi L,Raghunath M,Pandit A,Zeugolis DI

    更新日期:2015-03-04 00:00:00