Heurisztikusan gyorsított megerősítéses tanulási módszerek - áttekintés

A klasszikus megerősítéses tanulási módszerek (Q-learning, SARSA) mindegyike egy megfelelően definiált jutalomfüggvény által, a környezettől kapott visszajelzések ismeretében számos próbálkozással térképezi fel az adott probléma megoldásához vezető utat. A rendszer a tanulási folyamat kezdetén semmilyen tudással nem rendelkezik a probléma megoldásával kapcsolatban, a megoldás tudásbázisát a tanulási fázis során állítja elő, az a célja, hogy iterációról-iterációra feltérképezze azt. Ennek következtében azonban a tanulási folyamat, illetve a probléma megoldása alatt lejátszódó iterációk száma meglehetősen hosszadalmas lehet. Ez a folyamat felgyorsítható lehet abban az esetben, ha áll rendelkezésre részleges információ a megoldásra vonatkozóan és az injektálható a rendszerbe. A heurisztikusan gyorsított megerősítéses tanulási módszerek ember által, valamilyen formában megadott tudást visznek be rendszerbe, amely által a konvergenciasebesség és a megoldás alatt eltelt lépések száma csökkenhető. Jelen cikk célja, hogy áttekintse azon megerősítéses tanulási módszereket, melyek heurisztikusan gyorsítottak, azaz ember által megadott előzetes (a priori) illetve részleges tudásbázis injektálását teszik lehetővé a megerősítéses tanuló rendszerbe

A szenzoros információ párhuzamos feldolgozó mechanizmusai az emlősagyban = Paralell processing of sensory information in the mammalian brain

Élettani és anatómiai vizsgálataink egy olyan új koncepció bizonyítására irányulnak, mely szerint a szenzoros információ feldolgozása egymással párhuzamosan, egymástól többé-kevésbé függetlenül futó csatornákon/pályákon/áramlatokon keresztül valósul meg. A pályázat végrehajtása során altatott, immobilizált macskák agyában extracelluláris egysejt-tevékenységet regisztráltunk, valamint nyomkövető anyagokkal pályaanalízist végeztünk. Emellett éber, viselkedő majmok inferotemporális kérgében regisztráltunk egysejtaktivitást a képfelismerés élettani folyamatainak tisztázására. A vizsgálatok más része pszichiátriai, neurológiai vagy szemészeti kórképekben szenvedő embereken történt. Leírtuk, hogy a bazális ganglionok két magjában (nucleus caudatus és substantia nigra) levő sejtek klasszikus receptív mező tulajdonságai megfelelnek az általunk korábban leírt tecto-thalamo-corticalis multimodalis pályarendszer neuronjainak élettani sajátságaival. Morfológiai eredményeink összegzése és az élettani adatokkal történő összevetése alkalmat nyújt arra, hogy egy multimodalis szenzoros információfeldolgozó modellt állítsunk össze, mely a bazális ganglionok szenzoros bemenetének újszerű szemléletét szolgáltatja. A makákó majom inferotemporalis kérgi sejtjei egységtevékenységének mérése lehetővé tette a vizuális asszociatív funkció és percepciós neuronális működés összevetését is. | Our physiological and anatomical experiments were aimed at verifying a novel concept in sensory information processing. This concept implies that sensory information is processed through parallel, more or less independent channels/pathways/streams. We recorded extracellular single-unit activity in the brain of anaesthetized, immobilized cats and analyzed sensory pathways employing various tracers. In addition to this, single-unit activity was recorded in the inferotemporal cortex of awake, restrained monkeys in order to clarify the physiological processes during perception. Other experiments were performed in psychiatric, neurological and ophthalmologic patients. Our most important finding was that we proved the classical receptive field properties of some basal ganglia (caudate nucleus and substantia nigra) correspond to the physiological properties of neurons in the tecto-thalamo-cortical multimodal pathway described by us during the last 25 years. Integration of our morphological data with the results of physiological experiments allowed us to construct a novel model of sensory information processing that suggest the sensory input towards the basal ganglia being of tectal origin. The analysis of neuronal activity in the inferotemporal cortex of monkeys allowed a comparison of visual associative function and neuronal activity. In our clinical investigations we analyzed the consequences of selective pathway lesions in various disease forms

Unique Physicochemical Patterns of Residues in Protein-Protein Interfaces

Protein-protein interactions can be characterized by high-resolution structures of complexes, from which diverse features of the interfaces can be derived. For the majority of protein-protein interactions identified, however, there is no information on the structure of the complex or the interface involved in the interaction. Understanding what surface properties drive certain interactions is crucial in the functional evaluation of protein complexes. Here we show that the local patterning of the physicochemical properties of amino acids within surface patches is characteristic of interfaces. To describe this feature in a quantitative manner, we have defined a statistical potential, iPat, as a measure of surface patterning. iPat, which does not take evolutionary conservation or knowledge of the interaction partner into consideration, represents a function principally different from algorithms that consider intermolecular contacts. We assess its suitability for characterizing protein and peptide interfaces, and we demonstrate that iPat is uniquely descriptive for interfaces of proteins that undergo large conformational changes or that are involved in the binding of intrinsically disordered protein (IDP) partners. We suggest that as a stand-alone propensity or in combination with other features, iPat represents a new feature in analyzing the functional binding specificity of protein-protein interactions that has better predictive potential than other simple 1D features, such as hydrophobicity or stickiness

Breakdown of diameter selectivity in a reductive hydrogenation reaction of single-walled carbon nanotubes

Reductive hydrogenation was applied to two types of single-walled carbon nanotubes with different diameter range. Alkali metal intercalation, followed by reaction with methanol, led to hydrogenated products. Both yield and selectivity of this reaction showed strong dependence on diameter, contrary to expectation based on simple curvature effects. The observed yield, as detected by thermogravimetry-mass spectrometry and 1H-NMR, is drastically reduced in small-diameter tubes where the alkali dopant does not reach the inside of the bundles. Wide range optical transmission measurements were employed to determine the selectivity and indicate that besides higher yield, lower diameter selectivity occurs above a critical diameter

Wide-line NMR and DSC studies on intrinsically disordered p53 transactivation domain and its helically pre-structured segment

Wide-line 1H NMR intensity and differential scanning calorimetry measurements were carried out on the intrinsically disordered 73-residue full transactivation domain (TAD) of p53 tumor suppressor protein and two peptides, one a wild type p53 TAD peptide with a helix pre-structuring property and a mutant peptide with a disabled helix-forming propensity in order to characterize their water and ion binding characteristics. By quantifying the number of hydrate water molecules, we provide microscopic description for the interactions of water with a wild-type p53 TAD and two p53 TAD peptides. The results provide direct evidence that intrinsically disordered proteins (IDPs) and a less structured peptide not only have a higher hydration capacity than globular proteins but also are able to bind a larger amount of charged solute ions

Intrinsically Disordered Linkers Impart Processivity on Enzymes by Spatial Confinement of Binding Domains

(1) Background: Processivity is common among enzymes and mechanochemical motors that synthesize, degrade, modify or move along polymeric substrates, such as DNA, RNA, polysaccharides or proteins. Processive enzymes can make multiple rounds of modification without releasing the substrate/partner, making their operation extremely effective and economical. The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors. Processivity may also result from the kinetic bias of binding imposed by spatial confinement of two binding elements connected by an intrinsically disordered (ID) linker. (2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner. (3) Results: By analyzing 12 such proteins, such as cellulase, and RNAse-H, we illustrate that in these proteins linker length and flexibility, and the kinetic parameters of binding elements, are fine-tuned for optimizing processivity. We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size. (4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts

DisProt 7.0: a major update of the database of disordered proteins

The Database of Protein Disorder (DisProt, URL: www.disprot.org) has been significantly updated and upgraded since its last major renewal in 2007. The current release holds information on more than 800 entries of IDPs/IDRs, i.e. intrinsically disordered proteins or regions that exist and function without a well-defined three-dimensional structure. We have re-curated previous entries to purge DisProt from conflicting cases, and also upgraded the functional classification scheme to reflect continuous advance in the field in the past 10 years or so. We define IDPs as proteins that are disordered along their entire sequence, i.e. entirely lack structural elements, and IDRs as regions that are at least five consecutive residues without well-defined structure. We base our assessment of disorder strictly on experimental evidence, such as X-ray crystallography and nuclear magnetic resonance (primary techniques) and a broad range of other experimental approaches (secondary techniques). Confident and ambiguous annotations are highlighted separately. DisProt 7.0 presents classified knowledge regarding the experimental characterization and functional annotations of IDPs/IDRs, and is intended to provide an invaluable resource for the research community for a better understanding structural disorder and for developing better computational tools for studying disordered proteins

Discrete molecular dynamics can predict helical prestructured motifs in disordered proteins.

Intrinsically disordered proteins (IDPs) lack a stable tertiary structure, but their short binding regions termed Pre-Structured Motifs (PreSMo) can form transient secondary structure elements in solution. Although disordered proteins are crucial in many biological processes and designing strategies to modulate their function is highly important, both experimental and computational tools to describe their conformational ensembles and the initial steps of folding are sparse. Here we report that discrete molecular dynamics (DMD) simulations combined with replica exchange (RX) method efficiently samples the conformational space and detects regions populating alpha-helical conformational states in disordered protein regions. While the available computational methods predict secondary structural propensities in IDPs based on the observation of protein-protein interactions, our ab initio method rests on physical principles of protein folding and dynamics. We show that RX-DMD predicts alpha-PreSMos with high confidence confirmed by comparison to experimental NMR data. Moreover, the method also can dissect alpha-PreSMos in close vicinity to each other and indicate helix stability. Importantly, simulations with disordered regions forming helices in X-ray structures of complexes indicate that a preformed helix is frequently the binding element itself, while in other cases it may have a role in initiating the binding process. Our results indicate that RX-DMD provides a breakthrough in the structural and dynamical characterization of disordered proteins by generating the structural ensembles of IDPs even when experimental data are not available

DisProt

The Database of Protein Disorder (DisProt, URL: https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interface, a better search engine, a clearer API for programmatic access and a new annotation interface that integrates text mining technologies. The new entry format provides a greater flexibility, simplifies maintenance and allows the capture of more information from the literature. The new disorder ontology has been formalized and made interoperable by adopting the OWL format, as well as its structure and term definitions have been improved. The new annotation interface has made the curation process faster and more effective. We recently showed that new DisProt annotations can be effectively used to train and validate disorder predictors. We believe the growth of DisProt will accelerate, contributing to the improvement of function and disorder predictors and therefore to illuminate the 'dark' proteome