49 research outputs found
Secondary structure of globular proteins at the early and the final stages in protein folding
The ellipticities for an early transient intermediate in refolding observed by kinetic circular dichroism measurements at 220â225 nm for 14 different proteins are summarized, and the ellipticity values are compared with those for the final native proteins and also with the ellipticities expected from a physical theory of protein and polypeptide secondary structure. The results show that a substantial part of the protein secondary structure is in general formed in the earliest detectable intermediate in refolding and that the ellipticities in both the native and the intermediate states are consistent with the physical theory of protein secondary structure
Average and extreme multi-atom Van der Waals interactions: Strong coupling of multi-atom Van der Waals interactions with covalent bonding
<p>Abstract</p> <p>Background</p> <p>The prediction of ligand binding or protein structure requires very accurate force field potentials â even small errors in force field potentials can make a 'wrong' structure (from the billions possible) more stable than the single, 'correct' one. However, despite huge efforts to optimize them, currently-used all-atom force fields are still not able, in a vast majority of cases, even to keep a protein molecule in its native conformation in the course of molecular dynamics simulations or to bring an approximate, homology-based model of protein structure closer to its native conformation.</p> <p>Results</p> <p>A strict analysis shows that a specific coupling of multi-atom Van der Waals interactions with covalent bonding can, in extreme cases, increase (or decrease) the interaction energy by about 20â40% at certain angles between the direction of interaction and the covalent bond. It is also shown that on average multi-body effects decrease the total Van der Waals energy in proportion to the square root of the electronic component of dielectric permittivity corresponding to dipole-dipole interactions at small distances, where Van der Waals interactions take place.</p> <p>Conclusion</p> <p>The study shows that currently-ignored multi-atom Van der Waals interactions can, in certain instances, lead to significant energy effects, comparable to those caused by the replacement of atoms (for instance, C by N) in conventional pairwise Van der Waals interactions.</p
Regional variability in peatland burning at mid- to high-latitudes during the Holocene
Acknowledgements This work developed from the PAGES (Past Global Changes) C-PEAT (Carbon in Peat on EArth through Time) working group. PAGES has been supported by the US National Science Foundation, Swiss National Science Foundation, Swiss Academy of Sciences and Chinese Academy of Sciences. We acknowledge the following financial support: UK Natural Environment Research Council Training Grants NE/L002574/1 (T.G.S.) and NE/S007458/1 (R.E.F.); Dutch Foundation for the Conservation of Irish Bogs, Quaternary Research Association and Leverhulme Trust RPG-2021-354 (G.T.S); the Academy of Finland (M.V); PAI/SIA 80002 and FONDECYT IniciaciĂłn 11220705 - ANID, Chile (C.A.M.); R20F0002 (PATSER) ANID Chile (R.D.M.); Swedish Strategic Research Area (SRA) MERGE (ModElling the Regional and Global Earth system) (M.J.G.); Polish National Science Centre Grant number NCN 2018/29/B/ST10/00120 (K.A.); Russian Science Foundation Grant No. 19-14-00102 (Y.A.M.); University of Latvia Grant No. AAp2016/B041/Zd2016/AZ03 and the Estonian Science Council grant PRG323 (TrackLag) (N.S. and A.M.); U.S. Geological Survey Land Change Science/Climate Research & Development Program (M.J., L.A., and D.W.); German Research Foundation (DFG), grant MA 8083/2-1 (P.M.) and grant BL 563/19-1 (K.H.K.); German Academic Exchange Service (DAAD), grant no. 57044554, Faculty of Geosciences, University of MĂŒnster, and Bavarian University Centre for Latin America (BAYLAT) (K.H.K). Records from the Global Charcoal Database supplemented this work and therefore we would like to thank the contributors and managers of this open-source resource. We also thank Annica Greisman, Jennifer Shiller, Fredrik Olsson and Simon van Bellen for contributing charcoal data to our analyses. Any use of trade, firm, or product name is for descriptive purposes only and does not imply endorsement by the U.S. Government.Peer reviewedPostprin
CANDELS: The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey
The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS)
is designed to document the first third of galactic evolution, over the
approximate redshift (z) range 8--1.5. It will image >250,000 distant galaxies
using three separate cameras on the Hubble Space Telescope, from the
mid-ultraviolet to the near-infrared, and will find and measure Type Ia
supernovae at z>1.5 to test their accuracy as standardizable candles for
cosmology. Five premier multi-wavelength sky regions are selected, each with
extensive ancillary data. The use of five widely separated fields mitigates
cosmic variance and yields statistically robust and complete samples of
galaxies down to a stellar mass of 10^9 M_\odot to z \approx 2, reaching the
knee of the ultraviolet luminosity function (UVLF) of galaxies to z \approx 8.
The survey covers approximately 800 arcmin^2 and is divided into two parts. The
CANDELS/Deep survey (5\sigma\ point-source limit H=27.7 mag) covers \sim 125
arcmin^2 within GOODS-N and GOODS-S. The CANDELS/Wide survey includes GOODS and
three additional fields (EGS, COSMOS, and UDS) and covers the full area to a
5\sigma\ point-source limit of H \gtrsim 27.0 mag. Together with the Hubble
Ultra Deep Fields, the strategy creates a three-tiered "wedding cake" approach
that has proven efficient for extragalactic surveys. Data from the survey are
nonproprietary and are useful for a wide variety of science investigations. In
this paper, we describe the basic motivations for the survey, the CANDELS team
science goals and the resulting observational requirements, the field selection
and geometry, and the observing design. The Hubble data processing and products
are described in a companion paper.Comment: Submitted to Astrophysical Journal Supplement Series; Revised
version, subsequent to referee repor
CANDELS: The Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey - The Hubble Space Telescope Observations, Imaging Data Products and Mosaics
This paper describes the Hubble Space Telescope imaging data products and
data reduction procedures for the Cosmic Assembly Near-IR Deep Extragalactic
Legacy Survey (CANDELS). This survey is designed to document the evolution of
galaxies and black holes at , and to study Type Ia SNe beyond
. Five premier multi-wavelength sky regions are selected, each with
extensive multiwavelength observations. The primary CANDELS data consist of
imaging obtained in the Wide Field Camera 3 / infrared channel (WFC3/IR) and
UVIS channel, along with the Advanced Camera for Surveys (ACS). The
CANDELS/Deep survey covers \sim125 square arcminutes within GOODS-N and
GOODS-S, while the remainder consists of the CANDELS/Wide survey, achieving a
total of \sim800 square arcminutes across GOODS and three additional fields
(EGS, COSMOS, and UDS). We summarize the observational aspects of the survey as
motivated by the scientific goals and present a detailed description of the
data reduction procedures and products from the survey. Our data reduction
methods utilize the most up to date calibration files and image combination
procedures. We have paid special attention to correcting a range of
instrumental effects, including CTE degradation for ACS, removal of electronic
bias-striping present in ACS data after SM4, and persistence effects and other
artifacts in WFC3/IR. For each field, we release mosaics for individual epochs
and eventual mosaics containing data from all epochs combined, to facilitate
photometric variability studies and the deepest possible photometry. A more
detailed overview of the science goals and observational design of the survey
are presented in a companion paper.Comment: 39 pages, 25 figure
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNetÂź convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNetÂź model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery