Abstract:
:Modeling the dynamic nature of protein-ligand binding with atomistic simulations is one of the main challenges in computational biophysics, with important implications in the drug design process. Although in the past few years hardware and software advances have significantly revamped the use of molecular simulations, we still lack a fast and accurate ab initio description of the binding mechanism in complex systems, available only for up-to-date techniques and requiring several hours or days of heavy computation. Such delay is one of the main limiting factors for a larger penetration of protein dynamics modeling in the pharmaceutical industry. Here we present a game-changing technology, opening up the way for fast reliable simulations of protein dynamics by combining an adaptive reinforcement learning procedure with Monte Carlo sampling in the frame of modern multi-core computational resources. We show remarkable performance in mapping the protein-ligand energy landscape, being able to reproduce the full binding mechanism in less than half an hour, or the active site induced fit in less than 5 minutes. We exemplify our method by studying diverse complex targets, including nuclear hormone receptors and GPCRs, demonstrating the potential of using the new adaptive technique in screening and lead optimization studies.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Lecina D,Gilabert JF,Guallar Vdoi
10.1038/s41598-017-08445-5subject
Has Abstractpub_date
2017-08-16 00:00:00pages
8466issue
1issn
2045-2322pii
10.1038/s41598-017-08445-5journal_volume
7pub_type
杂志文章abstract::Since domestication, a large number of livestock breeds adapted to local conditions have been created by natural and artificial selection, representing one of the most powerful ways in which human groups have constructed niches to meet their need. Although many authors have described local breeds as the result of cult...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-24641-3
更新日期:2018-04-24 00:00:00
abstract::It is our contention that for multiscale modelling of infectious disease systems to evolve and expand in scope, it needs to be founded on a theory. Such a theory would improve our ability to describe infectious disease systems in terms of their scales and levels of organization, and their inter-relationships. In this ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-52820-3
更新日期:2019-11-08 00:00:00
abstract::Amyloid formation is associated with various pathophysiological conditions like Alzheimer's and Parkinson's diseases as well as many useful functions. The hallmark of amyloid assemblies is a conformational transition of the constituent proteins into a β - sheet rich filament. Accounting for this conformational transit...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep21103
更新日期:2016-02-17 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/s41598-019-44354-5
更新日期:2019-05-23 00:00:00
abstract::The association between cancer and volatile organic metabolites in exhaled breaths has attracted increasing attention from researchers. The present study reports on a systematic study of gas profiles of metabolites in human exhaled breath by pattern recognition methods. Exhaled breath was collected from 85 patients wi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep05383
更新日期:2014-06-20 00:00:00
abstract::Identification of mutants with impairments in auxin biosynthesis and dynamics by forward genetic screening is hindered by the complexity, redundancy and necessity of the pathways involved. Furthermore, although a few auxin-deficient mutants have been recently identified by screening for altered responses to shade, eth...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep11923
更新日期:2015-07-06 00:00:00
abstract::Realization of phosphor-free white-light emitters is becoming an important milestone on the road to achieve high quality and reliability in high-power white-light-emitting diodes (LEDs). However, most of reported methods have not been applied to practical use because of their difficulties and complexity. In this study...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep17372
更新日期:2015-12-02 00:00:00
abstract::Domestication and selective breeding has resulted in over 1000 extant cattle breeds. Many of these breeds do not excel in important traits but are adapted to local environments. These adaptations are a valuable source of genetic material for efforts to improve commercial breeds. As a step toward this goal we identifie...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-31304-w
更新日期:2018-08-28 00:00:00
abstract::Many environmental flow (e-flow) studies and applications have predominantly used state-(i.e., at a single time point) and rate-(i.e., temporal change) based demographic characteristics of species representing lower trophic levels (e.g., fish communities) to build flow-ecology relationships, rather than using a proces...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-79532-3
更新日期:2020-12-18 00:00:00
abstract::Emission of the trace gas dimethylsulphide (DMS) from the ocean influences the chemical and optical properties of the atmosphere, and the olfactory landscape for foraging marine birds, turtles and mammals. DMS concentration has been seen to vary across seasons and latitudes with plankton taxonomy and activity, and fol...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep32325
更新日期:2016-08-31 00:00:00
abstract::We report the results of an experiment on radio-tracking of individual grey field slugs in an arable field and associated data modelling designed to investigate the effect of slug population density in their movement. Slugs were collected in a commercial winter wheat field in which a 5x6 trapping grid had been establi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-74643-3
更新日期:2020-10-21 00:00:00
abstract::The group-IV tin has been hypothesized to possess intriguing electronic properties in an atom-thick hexagonal form. An attractive pathway of producing sizable 2D crystallites of tin is based on deintercalation of bulk compounds with suitable tin frameworks. Here, we have identified a new synthesizable metal distannide...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep28369
更新日期:2016-07-08 00:00:00
abstract::In this study, a rational combination of 200 pre-selected Carbohydrate-Active enzymes (CAZymes) and sulfatases were tested, individually or combined, according to their ability to degrade Chlorella vulgaris cell wall to access its valuable nutritional compounds. The disruption of microalgae cell walls by a four-enzyme...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-41775-0
更新日期:2019-03-29 00:00:00
abstract::Finding overlapping communities of complex networks remains a challenge in network science. To address this challenge, one of the widely used approaches is finding the communities of links by optimizing the objective function, partition density. In this study, we show that partition density suffers from inverse resolu...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-12432-1
更新日期:2017-09-29 00:00:00
abstract::Cancer hallmarks are evolutionary traits required by a tumour to develop. While extensively characterised, the way these traits are achieved through the accumulation of somatic mutations in key biological pathways is not fully understood. To shed light on this subject, we characterised the landscape of pathway alterat...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-25076-6
更新日期:2018-04-30 00:00:00
abstract::Although it has been reported that uterine signal transducer and activator of transcription 3 (STAT3) is essential for embryo implantation, the exact roles of uterine epithelial and stromal STAT3 on embryo implantation have not been elucidated. To address this issue, we generated Stat3-floxed/Ltf-iCre (Stat3-eKO), Sta...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-72640-0
更新日期:2020-09-23 00:00:00
abstract::We report a new family with autosomal dominant inheritance of a late onset rapidly progressive leukodystrophy in which exome sequencing has revealed a novel mutation p.R782G in the Colony-Stimulating Factor 1 Receptor gene (CSF1R). Neuropathology of two affected family members showed cerebral white matter degeneration...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep10042
更新日期:2015-05-15 00:00:00
abstract::Semen quality assessed by sperm count and sperm cell characteristics such as morphology and motility, is considered to be the main determinant of men's reproductive health. Therefore, sperm cell selection is vital in assisted reproductive technology (ART) used for the treatment of infertility. Conventional bright fiel...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-39523-5
更新日期:2019-03-05 00:00:00
abstract::Parvalbumin-containing projection neurons of the medial-septum-diagonal band of Broca ([Formula: see text]) are essential for hippocampal rhythms and learning operations yet are poorly understood at cellular and synaptic levels. We combined electrophysiological, optogenetic, and modeling approaches to investigate [For...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-80245-w
更新日期:2021-01-22 00:00:00
abstract::Nonstructural protein 1 (NS1) is secreted by dengue virus in the first days of infection and acts as an excellent dengue biomarker. Here, the direct electrical detection of NS1 from dengue type 2 virus has been achieved by the measurement of variations in open circuit potential (OCP) between a reference electrode and ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep07865
更新日期:2015-01-19 00:00:00
abstract::In vitro recapitulation of an organotypic stromal environment, enabling efficient angiogenesis, is crucial to investigate and possibly improve vascularization in regenerative medicine. Our study aims at engineering the complexity of a vascular milieu including multiple cell-types, a stromal extracellular matrix (ECM),...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-13882-3
更新日期:2017-10-27 00:00:00
abstract::People of north-eastern states of India consume raw areca-nut (RAN) and lime which could lead to oral, esophageal and gastric cancers. However, the incidence of these cancers are significantly lesser in those who consume pieces of Potentilla fulgens root along with RAN. Since evaluation of anticancer role, if any, of ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-53747-5
更新日期:2019-11-18 00:00:00
abstract::Exercise physiology is different in males and females. Females are poorly studied due to the complexity of the estrous cycle and this bias has created an exercise sex gap. Here, we evaluated the impact of sexual dimorphism and of the estrous cycle on muscle strength and running power of C57BL/6 mice. Like men, male mi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-29050-0
更新日期:2018-07-16 00:00:00
abstract::Spores of pathogenic fungi are virtually ubiquitous and cause human disease and severe losses in crops. The endophytic fungi Alternaria species produce host-selective phytotoxins. Alt a 1 is a strongly allergenic protein found in A. alternata that causes severe asthma. Despite the well-established pathogenicity of Alt...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep33468
更新日期:2016-09-16 00:00:00
abstract::Vitellogenesis or maternal yolk formation is considered critical to the reproduction of egg-laying animals. In invertebrates, however, most of its regulatory genes are still unknown. Via a combined mapping and whole-genome sequencing strategy, we performed a forward genetic screen to isolate novel regulators of yolk p...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep16381
更新日期:2015-11-10 00:00:00
abstract::Black phosphorus (BP) materials have attracted considerable attention owing to their ultra-sensitive humidity sensing characteristics because of the natural absorption of water (H2O) molecules on the BP surface caused by the specific 2D layer-crystalline structure. On the other hand, the BP-based humidity sensor is le...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-10848-3
更新日期:2017-09-05 00:00:00
abstract::Using a free boundary approach based on an analogy with ice melting models, we propose a deterministic PDE framework to describe the dynamics of fitness distributions in the presence of beneficial mutations with non-epistatic effects on fitness. Contrarily to most approaches based on deterministic models, our framewor...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-17212-5
更新日期:2017-12-19 00:00:00
abstract::We here describe the dc magnetic field over the human head produced by healthy hair follicles when the scalp is lightly pressed. This phenomenon was briefly reported decades earlier, where a double-planar SQUID (Superconducting Quantum Interference Devices) gradiometer at a single location was used. We here perform a ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-52110-y
更新日期:2019-10-30 00:00:00
abstract::Powdery mildew, a common cereal disease caused by the fungus Blumeria graminis, is a major limiting factor of barley production and genetic resistance is the most appropriate protection against it. To aid the breeding of new cultivars and their marketing, resistance genes can be postulated in homogeneous accessions. A...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-75978-7
更新日期:2020-11-03 00:00:00
abstract::This study aimed to identify single nucleotide polymorphisms (SNPs) associated with milk cholesterol (CHL) content via a genome wide association study (GWAS). Milk CHL content was determined by gas chromatography and expressed as mg of CHL in 100 g of fat (CHL_fat) or in 100 mg of milk (CHL_milk). GWAS was performed w...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-31427-0
更新日期:2018-09-05 00:00:00