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The weighted ensemble (WE) strategy has been demonstrated to be highly efficient in generating pathways and rate constants for rare events such as protein folding and protein binding using atomistic molecular dynamics simulations. Here we present two sets of tutorials instructing users in the best practices for preparing, carrying out, and analyzing WE simulations for various applications using the WESTPA software. The first set of more basic tutorials describes a range of simulation types, from a molecular association process in explicit solvent to more complex processes such as host-guest association, peptide conformational sampling, and protein folding. The second set ecompasses six advanced tutorials instructing users in the best practices of using key new features and plugins/extensions of the WESTPA 2.0 software package, which consists of major upgrades for larger systems and/or slower processes. The advanced tutorials demonstrate the use of the following key features: (i) a generalized resampler module for the creation of binless schemes, (ii) a minimal adaptive binning scheme for more efficient surmounting of free energy barriers, (iii) streamlined handling of large simulation datasets using an HDF5 framework, (iv) two different schemes for more efficient rate-constant estimation, (v) a Python API for simplified analysis of WE simulations, and (vi) plugins/extensions for Markovian Weighted Ensemble Milestoning and WE rule-based modeling for systems biology models. Applications of the advanced tutorials include atomistic and non-spatial models, and consist of complex processes such as protein folding and the membrane permeability of a drug-like molecule. Users are expected to already have significant experience with running conventional molecular dynamics or systems biology simulations.

Tropical cyclones (TCs) can cause severe wind and rain hazards. Unusual TC tracks and their extreme precipitation forecasts have become two difficult problems faced by conventional models of primitive equations. The case study in this paper finds that the numerical computation of the climatological component in conventional models restricts the prediction of unusual TC tracks. The climatological component should be a forcing quantity, not a predictor in the numerical integration of all models. Anomaly-based variable models can overcome the bottleneck of forecast time length or the one-week forecasting barrier, which is limited to less than one week for conventional models. The challenge in extreme precipitation forecasting is how to physically get the vertical velocity. The anomalous moisture stress modulus (AMSM), as an indicator of heavy rainfall presented in this paper, considers the two conditions associated with vertical velocity and anomalous specific humidity in the lower troposphere. Vertical velocity is produced by the orthogonal collision of horizontal anomalous airflows. [ABSTRACT FROM AUTHOR]

A record-breaking severe ozone (O3) pollution episode occurred in the Pearl River Delta (PRD) in early autumn 2019 when the PRD was under the influence of a Pacific subtropical high followed by Typhoon Mitag. In this study, we analyzed the effects of meteorological and photochemical processes on the O3 concentration in the PRD during this episode by carrying out the Weather Research Forecast–Community Multiscale Air Quality (WRF-CMAQ) model simulations. Results showed that low relative humidity, high boundary layer height, weak northerly surface wind, and strong downdrafts were the main meteorological factors contributing to O3 pollution. Moreover, delayed sea breezes that lasted into the night would transport O3 from the sea back to the land and resulted in secondary O3 maxima at night. In addition, O3 and its precursors stored in the residual layer above the surface layer at night can be mixed down to the surface in the next morning, further enhancing the daytime ground-level O3 concentration on the following day. Photochemical production of O3 , with a daytime average production rate of about 7.2 ppbh-1 (parts per billion), is found to be the predominate positive contributor to the O3 budget of the boundary layer (0–1260 m) during the entire O3 episode, while the horizontal and vertical transport fluxes are the dominant negative contributors. This O3 episode accounted for 10 out of the yearly total of 51 d when the maximum daily 8 h average (MDA8) O3 concentration exceeded the national standard of 75 ppb in the PRD in 2019. Based on these results, we propose that the enhanced photochemical production of O3 during the episode is a major cause of the most severe O3 pollution year since the official O3 observation started in the PRD in 2006. Moreover, since this O3 episode is a synoptic-scale phenomenon covering the entire eastern China, we also suggest that the enhanced photochemical production of O3 in this O3 episode is a major cause of the extraordinarily high O3 concentrations observed in eastern China in 2019. [ABSTRACT FROM AUTHOR]

To mark the 10th anniversary of the Melbourne Journal of International Law, we were inspired to reflect upon the past and to consider our future; to recall the scholarly contributions [...]

In this study, the seasonal variations of Madden-Julian Oscillation (MJO) are simulated with a 2.5-layer model governed by a set of perturbation equations, considering the effects of boundary layer friction convergence, diabatic heating, moisture feedback and background flow, under a non-resting basic state. The governing perturbation equations are written under a basic state defined by the 30-year climatology of observation (reanalysis), in which daily/monthly climatic wind, geopotential and moisture act as a background forcing influencing the evolution and propagation of MJO. Under this climatic background state, the precipitation of basic state is no longer zero but equal to the 30-year precipitation climatology, which is generally larger in the tropical region and has a dominant seasonal cycle in the subtropical region. Diabatic heating of convection is the key factor that produces the coupled Rossby-Kelvin structure of MJO and is a function of precipitation perturbation in the model. In common practice, precipitation perturbation can be derived from precipitation parametrization schemes, which usually consider only positive values during calculation because negative precipitation does not physically exist in the real world. However, the model in the study is run under a non-zero rainfall background, thus precipitation perturbation is not constraint to be non-negative. In this case, "negative precipitation" area is referred to as abnormally dry area, and leads to "diabatic cooling" (i.e. weaker diabatic heating compared to the basic state) to the troposphere.Model simulations show that the climatic state and "negative precipitation" are two indispensable factors to the MJO seasonal variations. The climatic state provides a crucial background circulation and moisture distribution that favors MJOs / Boreal Summer Intraseasonal Oscillations (BSISOs), as reported in previous studies. On top of the climatic state, our results indicate that the "negative precipitation" effect is also essential to the simulation of MJO in different seasons. The MJO seasonal variations are less obvious if the model only incorporates positive precipitation. Results also reveal that the "negative precipitation" effectively damps shortwaves. [ABSTRACT FROM AUTHOR]

Sequence-encoded protein folding is a ubiquitous biological process that has been successfully engineered in a range of oligomeric molecules with artificial backbone chemical connectivity. A remarkable aspect of protein folding is the contrast between the rapid rates at which most sequences in nature fold and the vast number of conformational states possible in an unfolded chain with hundreds of rotatable bonds. Research efforts spanning several decades have sought to elucidate the fundamental chemical principles that dictate the speed and mechanism of natural protein folding. In contrast, little is known about how protein mimetic entities transition between an unfolded and folded state. Here, we report effects of altered backbone connectivity on the folding kinetics and mechanism of the B domain of Staphylococcal protein A (BdpA), an ultrafast-folding sequence. A combination of experimental biophysical analysis and atomistic molecular dynamics simulations performed on the prototype protein and several heterogeneous-backbone variants reveal the interplay among backbone flexibility, folding rates, and structural details of the transition state ensemble. Collectively, these findings suggest a significant degree of plasticity in the mechanisms that can give rise to ultrafast folding in the BdpA sequence and provide atomic level insights into how protein mimetic chains adopt an ordered folded state., Competing Interests: L. T. C. is a member of the Scientific Advisory Board of OpenEye Scientific, Cadence Molecular Sciences; and an Open Science Fellow with Psivant Therapeutics., (This journal is © The Royal Society of Chemistry.)