Binding Modes of Ligands Using Enhanced Sampling (BLUES): Rapid Decorrelation of Ligand Binding Modes Using Nonequilibrium Candidate Monte Carlo

<div>Accurately predicting protein-ligand binding is a major goal in computational chemistry, but even the prediction of ligand binding modes in proteins poses major challenges. Here, we focus on solving the binding mode prediction problem for rigid fragments. That is, we focus on computing the dominant placement, conformation, and orientations of a relatively rigid, fragment-like ligand in a receptor, and the populations of the multiple binding modes which may be relevant. This problem is important in its own right, but is even more timely given the recent success of alchemical free energy calculations. Alchemical calculations are increasingly used to predict binding free energies of ligands to receptors. However, the accuracy of these calculations is dependent on proper sampling of the relevant ligand binding modes. Unfortunately, ligand binding modes may often be uncertain, hard to predict, and/or slow to interconvert on simulation timescales, so proper sampling with current techniques can require prohibitively long simulations. We need new methods which dramatically improve sampling of ligand binding modes. Here, we develop and apply a nonequilibrium candidate Monte Carlo (NCMC) method to improve sampling of ligand binding modes.</div><div><br></div><div>In this technique the ligand is rotated and subsequently allowed to relax in its new position through alchemical perturbation before accepting or rejecting the rotation and relaxation as a nonequilibrium Monte Carlo move. When applied to a T4 lysozyme model binding system, this NCMC method shows over two orders of magnitude improvement in binding mode sampling efficiency compared to a brute force molecular dynamics simulation. This is a first step towards applying this methodology to pharmaceutically relevant binding of fragments and, eventually, drug-like molecules. We are making this approach available via our new Binding Modes of Ligands using Enhanced Sampling (BLUES) package which is freely available on GitHub.</div

NGTS clusters survey – IV. Search for Dipper stars in the Orion Nebular Cluster

The dipper is a novel class of young stellar object associated with large drops in flux on the order of 10–50 per cent lasting for hours to days. Too significant to arise from intrinsic stellar variability, these flux drops are currently attributed to disc warps, accretion streams, and/or transiting circumstellar dust. Dippers have been previously studied in young star-forming regions, including the Orion Complex. Using Next Generation Transit Survey (NGTS) data, we identified variable stars from their light curves. We then applied a machine learning random forest classifier for the identification of new dipper stars in Orion using previous variable classifications as a training set. We discover 120 new dippers, of which 83 are known members of the Complex. We also investigated the occurrence rate of discs in our targets, again using a machine learning approach. We find that all dippers have discs, and most of these are full discs. We use dipper periodicity and model-derived stellar masses to identify the orbital distance to the inner disc edge for dipper objects, confirming that dipper stars exhibit strongly extended sublimation radii, adding weight to arguments that the inner disc edge is further out than predicted by simple models. Finally, we determine a dipper fraction (the fraction of stars with discs which are dippers) for known members of 27.8 ± 2.9 per cent. Our findings represent the largest population of dippers identified in a single cluster to date.</p

NGTS clusters survey -- II. White-light flares from the youngest stars in Orion

We present the detection of high energy white-light flares from pre-main sequence stars associated with the Orion complex, observed as part of the Next Generation Transit Survey (NGTS). With energies up to 5.2 × 1035 erg these flares are some of the most energetic white-light flare events seen to date. We have used the NGTS observations of flaring and non-flaring stars to measure the average flare occurrence rate for 4 Myr M0-M3 stars. We have also combined our results with those from previous studies to predict average rates for flares above 1 × 1035 ergs for early M stars in nearby young associations

Stellar flares detected with the Next Generation Transit Survey

We present the results of a search for stellar flares in the first data release from the Next Generation Transit Survey (NGTS). We have found 610 flares from 339 stars, with spectral types between F8 and M6, the majority of which belong to the Galactic thin disc. We have used the 13-s cadence NGTS light curves to measure flare properties such as the flare amplitude, duration, and bolometric energy. We have measured the average flare occurrence rates of K and early to mid-M stars and present a generalized method to measure these rates while accounting for changing detection sensitivities. We find that field age K and early M stars show similar flare behaviour, while fully convective M stars exhibit increased white-light flaring activity, which we attribute to their increased spin-down time. We have also studied the average flare rates of pre-main-sequence K and M stars, showing they exhibit increased flare activity relative to their main-sequence counterparts

Simultaneous TESS and NGTS Transit Observations of WASP-166b

We observed a transit of WASP-166 b using nine NGTS telescopes simultaneously with TESS observations of the same transit. We achieved a photometric precision of 152 ppm per 30 minutes with the nine NGTS telescopes combined, matching the precision reached by TESS for the transit event around this bright (T=8.87) star. The individual NGTS light curve noise is found to be dominated by scintillation noise and appears free from any time-correlated noise or any correlation between telescope systems. We fit the NGTS data for $T_C$ and $R_p/R_*$. We find $T_C$ to be consistent to within 0.25$\sigma$ of the result from the TESS data, and the difference between the TESS and NGTS measured $R_p/R_*$ values is 0.9$\sigma$. This experiment shows that multi-telescope NGTS photometry can match the precision of TESS for bright stars, and will be a valuable tool in refining the radii and ephemerides for bright TESS candidates and planets. The transit timing achieved will also enable NGTS to measure significant transit timing variations in multi-planet systems

NGTS and WASP photometric recovery of a single-transit candidate from TESS

The Transiting Exoplanet Survey Satellite (TESS) produces a large number of single-transit event candidates, since the mission monitors most stars for only ∼27d. Such candidates correspond to long-period planets or eclipsing binaries. Using the TESS Sector 1 full-frame images, we identified a 7750 ppm single-transit event with a duration of 7 h around the moderately evolved F-dwarf star TIC-238855958 (Tmag = 10.23, Teff = 6280 ± 85 K). Using archival WASP photometry we constrained the true orbital period to one of three possible values. We detected a subsequent transit-event with NGTS, which revealed the orbital period to be 38.20 d. Radial velocity measurements from the CORALIE Spectrograph show the secondary object has a mass of M2 = 0.148 ± 0.003M⊙, indicating this system is an F-M eclipsing binary. The radius of the M-dwarf companion is R2 = 0.171 ± 0.003 R⊙, making this one of the most well characterized stars in this mass regime. We find that its radius is 2.3σ lower than expected from stellar evolution models

TIC-320687387 B: a long-period eclipsing M-dwarf close to the hydrogen burning limit

We are using precise radial velocities from CORALIE together with precision photometry from the Next Generation Transit Survey (NGTS) to follow-up stars with single-transit events detected with the Transiting Exoplanet Survey Satellite (TESS). As part of this survey, we identified a single transit on the star TIC-320687387, a bright (T = 11.6) G-dwarf observed by TESS in Sectors 13 and 27. From subsequent monitoring of TIC-320687387 with CORALIE, NGTS, and Lesedi we determined that the companion, TIC-320687387 B, is a very low-mass star with a mass of 96.2±1.92.0 MJ and radius of 1.14±0.020.02 RJ placing it close to the hydrogen burning limit (∼80 MJ). TIC-320687387 B is tidally decoupled and has an eccentric orbit, with a period of 29.77381 d and an eccentricity of 0.366 ± 0.003. Eclipsing systems such as TIC-320687387 AB allow us to test stellar evolution models for low-mass stars, which in turn are needed to calculate accurate masses and radii for exoplanets orbiting single low-mass stars. The sizeable orbital period of TIC-320687387 B makes it particularly valuable as its evolution can be assumed to be free from perturbations caused by tidal interactions with its G-type host star.</p

NGTS clusters survey - III. A low-mass eclipsing binary in the Blanco 1 open cluster spanning the fully convective boundary

We present the discovery and characterization of an eclipsing binary identified by the Next Generation Transit Survey in the ∼115-Myr-old Blanco 1 open cluster. NGTS J0002-29 comprises three M dwarfs: a short-period binary and a companion in a wider orbit. This system is the first well-characterized, low-mass eclipsing binary in Blanco 1. With a low mass ratio, a tertiary companion, and binary components that straddle the fully convective boundary, it is an important benchmark system, and one of only two well-characterized, low-mass eclipsing binaries at this age. We simultaneously model light curves from NGTS, TESS, SPECULOOS, and SAAO, radial velocities from VLT/UVES and Keck/HIRES, and the system’s spectral energy distribution. We find that the binary components travel on circular orbits around their common centre of mass in Porb = 1.098 005 24 ± 0.000 000 38 d, and have masses Mpri = 0.3978 ± 0.0033 M☉ and Msec = 0.2245 ± 0.0018 M☉, radii Rpri = 0.4037 ± 0.0048 R☉ and Rsec = 0.2759 ± 0.0055 R☉, and effective temperatures Tpri = 3372+44-37 K and Tsec = 3231+38-31 K. We compare these properties to the predictions of seven stellar evolution models, which typically imply an inflated primary. The system joins a list of 19 well-characterized, low-mass, sub-Gyr, stellar-mass eclipsing binaries, which constitute some of the strongest observational tests of stellar evolution theory at low masses and young ages

NGTS-21b: an inflated Super-Jupiter orbiting a metal-poor K dwarf

We report the discovery of NGTS-21b , a massive hot Jupiter orbiting a low-mass star as part of the Next Generation Transit Survey (NGTS). The planet has a mass and radius of 2.36 ± 0.21 MJ and 1.33 ± 0.03 RJ, and an orbital period of 1.543 d. The host is a K3V (Teff = 4660 ± 41 K) metal-poor ([Fe/H] = −0.26 ± 0.07 dex) dwarf star with a mass and radius of 0.72 ± 0.04 M⊙ and 0.86 ± 0.04R⊙. Its age and rotation period of 10.02+3.29−7.30 Gyr and 17.88 ± 0.08 d, respectively, are in accordance with the observed moderately low-stellar activity level. When comparing NGTS-21b with currently known transiting hot Jupiters with similar equilibrium temperatures, it is found to have one of the largest measured radii despite its large mass. Inflation-free planetary structure models suggest the planet’s atmosphere is inflated by ∼21 per cent⁠, while inflationary models predict a radius consistent with observations, thus pointing to stellar irradiation as the probable origin of NGTS-21b’s radius inflation. Additionally, NGTS-21b’s bulk density (1.25 ± 0.15 g cm–3) is also amongst the largest within the population of metal-poor giant hosts ([Fe/H] < 0.0), helping to reveal a falling upper boundary in metallicity–planet density parameter space that is in concordance with core accretion formation models. The discovery of rare planetary systems such as NGTS-21 greatly contributes towards better constraints being placed on the formation and evolution mechanisms of massive planets orbiting low-mass stars.</p

NGTS-19b: a high-mass transiting brown dwarf in a 17-d eccentric orbit

We present the discovery of NGTS-19b, a high mass transiting brown dwarf discovered by the Next Generation Transit Survey (NGTS). We investigate the system using follow up photometry from the South African Astronomical Observatory, as well as sector 11 TESS data, in combination with radial velocity measurements from the CORALIE spectrograph to precisely characterise the system. We find that NGTS-19b is a brown dwarf companion to a K-star, with a mass of $69.5 ^{+5.7}_{-5.4}$ M$_{Jup}$ and radius of $1.034 ^{+0.055}_{-0.053}$ R$_{Jup}$. The system has a reasonably long period of 17.84 days, and a high degree of eccentricity of $0.3767 ^{+0.0061}_{-0.0061}$. The mass and radius of the brown dwarf imply an age of $0.46 ^{+0.26}_{-0.15}$ Gyr, however this is inconsistent with the age determined from the host star SED, suggesting that the brown dwarf may be inflated. This is unusual given that its large mass and relatively low levels of irradiation would make it much harder to inflate. NGTS-19b adds to the small, but growing number of brown dwarfs transiting main sequence stars, and is a valuable addition as we begin to populate the so called brown dwarf desert