Viral genomes, functional genes, and microbial genomes of 144 activated sludge samples taken from 54 WWTPs across 13 countries on a global scale

The study dataset contains 85,114 viral genomes, 1,115,185 viral functional genes, and 3,823 microbial genomes obtained from 54 WWTPs across 13 countries. Note: The manuscript that produced this dataset is currently being processed. Please avoid using the data for academic publication until the manuscript has completed its peer-review process

Sampling conformational space of intrinsically disordered proteins in explicit solvent: Comparison between well-tempered ensemble approach and solute tempering method

Intrinsically disordered proteins (IDPs) are a class of proteins that expected to be largely unstructured under physiological conditions. Due to their heterogeneous nature, experimental characterization of IDP is challenging. Temperature replica exchange molecular dynamics (T-REMD) is a widely used enhanced sampling method to probe structural characteristics of these proteins. However, its application has been hindered due to its tremendous computational cost, especially when simulating large systems in explicit solvent. Two-methods, parallel tempering well-tempered-ensemble-(PT-WTE) and replica-exchange-with solute tempering (REST), have been proposed to alleviate the computational expense of T-REMD. In this work, we select three different IDP systems to compare the sampling characteristics and efficiencies of the two methods Both the two methods could efficiently sample the conformational space of IDP and yield highly consistent results for all the three IDPs. The efficiencies of the two methods: are compatible, with about 5-6 times better than the plain T-REMD. Besides, the advantages and disadvantages of each method are also discussed. Specially, the PT-WTE method could provide temperature dependent data of the system which could not be achieved by REST, while the REST method could readily be used to a part of the system, which is quite efficient to simulate some biological processes. (C) 2016 Elsevier Inc. All rights reserved.</p

Compromise in competition between free energy and binding effect of intrinsically disordered protein p53 C-terminal domain

The C-terminal domain (CTD) of tumour suppressor p53 is an intrinsically disordered protein which has been shown to be able to bind multiple partner proteins and exercise diverse physiological functions in the cell. In this study, we performed molecular dynamics simulations on the isolated p53 CTD, as well as three regulatory binding complexes to investigate the conformational ensemble of isolated p53 CTD and its dynamic structures when different binding partner present. The results demonstrate that the isolated p53 CTD resembles a molten globule rather than extended structure. It mainly adopts random coil conformations with some tendency to form helical structures, which is consistent with experimental observations. For isolated p53 CTD, the dynamics is exclusively dominated by the intrinsic free energy and the p53 CTD could not folded spontaneously to each binding competent state which is located in high free energy region. However, when the binding partners present, the dynamics of p53 CTD are dominated by two mechanisms, the p53 CTD tending to adopt the structure with minimum free energy as isolate existed and the binding energy from partner protein tending to minimum. Each of them has an extreme tendency and corresponds to a possible characteristic state, the random coil state and each binding competent state. The compromise in competition between these two mechanisms results in alternate realisation of different characteristic states, while the relative strength of each mechanism determines the sampling frequency of each characteristic state.</p

The principle of compromise in competition: exploring stability condition of protein folding

Thermodynamic hypothesis and kinetic stability are currently used to understand protein folding. The former assumes that free energy minimum is the exclusive dominant mechanism in most cases, while the latter shows that some proteins have even lower free energy in intermediate states and their native states are kinetically trapped in the higher free energy region. This article explores the stability condition of protein structures on the basis of our study of complex chemical systems. We believe that separating one from another is not reasonable since they should be coupled, and protein structures should be dominated by at least two mechanisms resulting in different characteristic states. It is concluded that: (1) Structures of proteins are dynamic, showing multiple characteristic states emerging alternately and each dominated by a respective mechanism. (2) Compromise in competition of multiple dominant mechanisms might be the key to understanding the stability of protein structures. (3) The dynamic process of protein folding should be depicted through the time series of both its energetic and structural changes, which is much meaningful and applicable than the free energy landscape

Simulation of coupled folding and binding of an intrinsically disordered protein in explicit solvent with metadynamics

The C-terminal domain of measles virus nucleoprotein is an intrinsically disordered protein that could bind to the X domain (XD) of phosphoprotein P to exert its physiological function. Experiments reveal that the minimal binding unit is a 21-residue alpha-helical molecular recognition element (alpha-MORE-MeV), which adopts a fully helical conformation upon binding to XD. Due to currently limited computing power, direct simulation of this coupled folding and binding process with atomic force field in explicit solvent cannot be achieved. In this work, two advanced sampling methods, metadynamics and parallel tempering, are combined to characterize the free energy surface of this process and investigate the underlying mechanism. Starting from an unbound and partially folded state of alpha-MoRE-MeV, multiple folding and binding events are observed during the simulation and the energy landscape was well estimated. The results demonstrate that the isolated alpha-MORE-MeV resembles a molten globule and rapidly interconverts between random coil and multiple partially helical states in solution. The coupled folding and binding process occurs through the induced fit mechanism, with the residual helical conformations providing the initial binding sites. Upon binding, alpha-MORE-MeV can easily fold into helical conformation without obvious energy barriers. Two mechanisms, namely, the system tending to adopt the structure in which the free energy of isolated alpha-MORE-MeV is the minimum, and the binding energy of alpha-MoRE-MeV to its partner protein XD tending to the minimum, jointly dominate the coupled folding and binding process. With the advanced sampling approach, more IDP systems could be simulated and common mechanisms concerning the coupled folding and binding process could be investigated in the future. (C) 2016 Published by Elsevier Inc.</p

Simulations of flow induced structural transition of the beta-switch region of glycoprotein Ib alpha

Binding of glycoprotein Ib alpha to von Willebrand factor induces platelet adhesion to injured vessel walls and initiates a multistep hemostatic process. It has been hypothesized that the flow condition could induce a loop to beta-sheet conformational change in the beta-switch region of glycoprotein Ib alpha, which regulates it binding to the von Willebrand factor and facilitates the blood clot formation and wound healing. In this work, direct molecular dynamics (MD), flow MD and metadynamics, were employed to investigate the mechanisms of this flow induced conformational transition process. Specifically, the free energy landscape of the whole transition process was drawn by metadynamics with the path collective variable approach. The results reveal that without flow, the free energy landscape has two main basins, including a random loop basin stabilized by large conformational entropy and a partially folded beta-sheet basin. The free energy barrier separating these two basins is relatively high and the beta-switch could not fold from loop to beta-sheet state spontaneously. The fully beta-sheet conformations located in high free energy regions, which are also unstable and gradually unfold into partially folded beta-sheet state with flow. Relatively weak flow could trigger some folding of the beta-switch but could not fold it into fully beta-sheet state. Under strong flow conditions, the beta-switch could readily overcome the high free energy barrier and fold into fully beta-sheet state. (C) 201 5 Elsevier B.V. All rights reserved

Global diversity and biogeography of DNA viral communities in activated sludge systems

Abstract Background Activated sludge (AS) systems in wastewater treatment plants (WWTPs) harbor enormous viruses that regulate microbial metabolism and nutrient cycling, significantly influencing the stability of AS systems. However, our knowledge about the diversity of viral taxonomic groups and functional traits in global AS systems is still limited. To address this gap, we investigated the global diversity and biogeography of DNA viral communities in AS systems using 85,114 viral operational taxonomic units (vOTUs) recovered from 144 AS samples collected across 54 WWTPs from 13 different countries. Results AS viral communities and their functional traits exhibited distance-decay relationship (DDR) at the global scale and latitudinal diversity gradient (LDG) from equator to mid-latitude. Furthermore, it was observed that AS viral community and functional gene structures were largely driven by the geographic factors and wastewater types, of which the geographic factors were more important. Carrying and disseminating auxiliary metabolic genes (AMGs) associated with the degradation of polysaccharides, sulfate reduction, denitrification, and organic phosphoester hydrolysis, as well as the lysis of crucial functional microbes that govern biogeochemical cycles were two major ways by which viruses could regulate AS functions. It was worth noting that our study revealed a high abundance of antibiotic resistance genes (ARGs) in viral genomes, suggesting that viruses were key reservoirs of ARGs in AS systems. Conclusions Our results demonstrated the highly diverse taxonomic groups and functional traits of viruses in AS systems. Viral lysis of host microbes and virus-mediated HGT can regulate the biogeochemical and nutrient cycles, thus affecting the performance of AS systems. These findings provide important insights into the viral diversity, function, and ecology in AS systems on a global scale. Video Abstrac

Tundra Soil Viruses Mediate Responses of Microbial Communities to Climate Warming

The rise of global temperature causes the degradation of the substantial reserves of carbon (C) stored in tundra soils, in which microbial processes play critical roles. Viruses are known to influence the soil C cycle by encoding auxiliary metabolic genes and infecting key microorganisms, but their regulation of microbial communities under climate warming remains unexplored. In this study, we evaluated the responses of viral communities for about 5 years of experimental warming at two depths (15 to 25 cm and 45 to 55 cm) in the Alaskan permafrost region. Our results showed that the viral community and functional gene composition and abundances (including viral functional genes related to replication, structure, infection, and lysis) were significantly influenced by environmental conditions such as total nitrogen (N), total C, and soil thawing duration. Although long-term warming did not impact the viral community composition at the two depths, some glycoside hydrolases encoded by viruses were more abundant at both depths of the warmed plots. With the continuous reduction of total C, viruses may alleviate methane release by altering infection strategies on methanogens. Importantly, viruses can adopt lysogenic and lytic lifestyles to manipulate microbial communities at different soil depths, respectively, which could be one of the major factors causing the differences in microbial responses to warming. This study provides a new ecological perspective on how viruses regulate the responses of microbes to warming at community and functional scales. IMPORTANCE Permafrost thawing causes microbial release of greenhouse gases, exacerbating climate warming. Some previous studies examined the responses of the microbial communities and functions to warming in permafrost region, but the roles of viruses in mediating the responses of microbial communities to warming are poorly understood. This study revealed that warming induced changes in some viral functional classes and in the virus/microbe ratios for specific lineages, which might influence the entire microbial community. Furthermore, differences in viral communities and functions, along with soil depths, are important factors influencing microbial responses to warming. Collectively, our study revealed the regulation of microbial communities by viruses and demonstrated the importance of viruses in the microbial ecology research