Abstract
Protein–protein interactions play a crucial role in all cellular functions and biological processes and mutations leading to their disruption are enriched in many diseases. While a number of ...computational methods to assess the effects of variants on protein–protein binding affinity have been proposed, they are in general limited to the analysis of single point mutations and have been shown to perform poorly on independent test sets. Here, we present mmCSM-PPI, a scalable and effective machine learning model for accurately assessing changes in protein–protein binding affinity caused by single and multiple missense mutations. We expanded our well-established graph-based signatures in order to capture physicochemical and geometrical properties of multiple wild-type residue environments and integrated them with substitution scores and dynamics terms from normal mode analysis. mmCSM-PPI was able to achieve a Pearson's correlation of up to 0.75 (RMSE = 1.64 kcal/mol) under 10-fold cross-validation and 0.70 (RMSE = 2.06 kcal/mol) on a non-redundant blind test, outperforming existing methods. Our method is freely available as a user-friendly and easy-to-use web server and API at http://biosig.unimelb.edu.au/mmcsm_ppi.
Graphical Abstract
Graphical Abstract
mmCSM-PPI: predicting the effects of multiple point mutations on protein–protein interactions.
IslandViewer (http://pathogenomics.sfu.ca/islandviewer) is a widely used web-based resource for the prediction and analysis of genomic islands (GIs) in bacterial and archaeal genomes. GIs are ...clusters of genes of probable horizontal origin, and are of high interest since they disproportionately encode genes involved in medically and environmentally important adaptations, including antimicrobial resistance and virulence. We now report a major new release of IslandViewer, since the last release in 2013. IslandViewer 3 incorporates a completely new genome visualization tool, IslandPlot, enabling for the first time interactive genome analysis and gene search capabilities using synchronized circular, horizontal and vertical genome views. In addition, more curated virulence factors and antimicrobial resistance genes have been incorporated, and homologs of these genes identified in closely related genomes using strict filters. Pathogen-associated genes have been re-calculated for all pre-computed complete genomes. For user-uploaded genomes to be analysed, IslandViewer 3 can also now handle incomplete genomes, with an improved queuing system on compute nodes to handle user demand. Overall, IslandViewer 3 represents a significant new version of this GI analysis software, with features that may make it more broadly useful for general microbial genome analysis and visualization.
Abstract
Increasing evidence proves the essential regulatory roles of non-coding RNAs (ncRNAs) in biological processes. However, characterizing the specific functions of ncRNAs remains a challenging ...task, owing to the intensive consumption of the experimental approaches. Here, we present an online platform ncFANs v2.0 that is a significantly enhanced version of our previous ncFANs to provide multiple computational methods for ncRNA functional annotation. Specifically, ncFANs v2.0 was updated to embed three functional modules, including ncFANs-NET, ncFANs-eLnc and ncFANs-CHIP. ncFANs-NET is a new module designed for data-free functional annotation based on four kinds of pre-built networks, including the co-expression network, co-methylation network, long non-coding RNA (lncRNA)-centric regulatory network and random forest-based network. ncFANs-eLnc enables the one-stop identification of enhancer-derived lncRNAs from the de novo assembled transcriptome based on the user-defined or our pre-annotated enhancers. Moreover, ncFANs-CHIP inherits the original functions for microarray data-based functional annotation and supports more chip types. We believe that our ncFANs v2.0 carries sufficient convenience and practicability for biological researchers and facilitates unraveling the regulatory mechanisms of ncRNAs. The ncFANs v2.0 server is freely available at http://bioinfo.org/ncfans or http://ncfans.gene.ac.
Graphical Abstract
Graphical abstract
The workflow of ncFANs v2.0.
This guide will get you up and running with Azure DevOps Services to implement DevOps practices like configuration management, release management, continuous integration, infrastructure as code, and ...application monitoring.
Abstract
The IntFOLD server based at the University of Reading has been a leading method over the past decade in providing free access to accurate prediction of protein structures and functions. In a ...post-AlphaFold2 world, accurate models of tertiary structures are widely available for even more protein targets, so there has been a refocus in the prediction community towards the accurate modelling of protein-ligand interactions as well as modelling quaternary structure assemblies. In this paper, we describe the latest improvements to IntFOLD, which maintains its competitive structure prediction performance by including the latest deep learning methods while also integrating accurate model quality estimates and 3D models of protein-ligand interactions. Furthermore, we also introduce our two new server methods: MultiFOLD for accurately modelling both tertiary and quaternary structures, with performance which has been independently verified to outperform the standard AlphaFold2 methods, and ModFOLDdock, which provides world-leading quality estimates for quaternary structure models. The IntFOLD7, MultiFOLD and ModFOLDdock servers are available at: https://www.reading.ac.uk/bioinf/.
Graphical Abstract
Graphical Abstract
Prediction of protein, structures, functions and interactions at the University of Reading using the IntFOLD7, MultFOLD and ModFOLDdock servers.
Abstract
The Orthology Benchmark Service (https://orthology.benchmarkservice.org) is the gold standard for orthology inference evaluation, supported and maintained by the Quest for Orthologs ...consortium. It is an essential resource to compare existing and new methods of orthology inference (the bedrock for many comparative genomics and phylogenetic analysis) over a standard dataset and through common procedures. The Quest for Orthologs Consortium is dedicated to maintaining the resource up to date, through regular updates of the Reference Proteomes and increasingly accessible data through the OpenEBench platform. For this update, we have added a new benchmark based on curated orthology assertion from the Vertebrate Gene Nomenclature Committee, and provided an example meta-analysis of the public predictions present on the platform.
Graphical Abstract
Graphical Abstract
The Quest for Orthologs benchmarking service helps orthology inference methods developers compare their methods on standardized benchmarks, users to choose appropriate methods and provides data for consensus orthology calls.
A new section of databases and programs devoted to double crystallographic groups (point and space groups) has been implemented in the Bilbao Crystallographic Server (http://www.cryst.ehu.es). The ...double crystallographic groups are required in the study of physical systems whose Hamiltonian includes spin‐dependent terms. In the symmetry analysis of such systems, instead of the irreducible representations of the space groups, it is necessary to consider the single‐ and double‐valued irreducible representations of the double space groups. The new section includes databases of symmetry operations (DGENPOS) and of irreducible representations of the double (point and space) groups (REPRESENTATIONS DPG and REPRESENTATIONS DSG). The tool DCOMPREL provides compatibility relations between the irreducible representations of double space groups at different k vectors of the Brillouin zone when there is a group–subgroup relation between the corresponding little groups. The program DSITESYM implements the so‐called site‐symmetry approach, which establishes symmetry relations between localized and extended crystal states, using representations of the double groups. As an application of this approach, the program BANDREP calculates the band representations and the elementary band representations induced from any Wyckoff position of any of the 230 double space groups, giving information about the properties of these bands. Recently, the results of BANDREP have been extensively applied in the description of and the search for topological insulators.
A new section of computer tools devoted to the double crystallographic groups has been implemented in the Bilbao Crystallographic Server (http://www.cryst.ehu.es). The section includes databases of symmetry operations and irreducible representations of the double point and space groups and programs that compute the compatibility relations, generate relevant information related to the site‐symmetry approach, and calculate band representations and elementary band representations induced from any Wyckoff position of any double space group.
This investigation was performed to obtain a promising phytase enzyme producing yeast. In this regard, the PSM was used to isolate the phytase-producing Hanseniaspora guilliermondii S1 (MG663578) ...from sugarcane juice. The SSF optimum conditions for phytase generation were optimized using (OVAT) one-variable-at-a-time strategy using both Box-Behnken design and shake flask method (g/100 ml: 0.05 yeast extract, 0.15 Peptone, 0.05 malt extract 0.50 dextrose, pH 5.8 and 28ᵒC). The protein model developed was shown to be adequate for phytase production (91% accuracy), with the greatest phytase productivity in shake flask with substrate jack fruit seed powder being 395 ± 0.43 U/ml compared to 365U/ml for the BBD projected value. Crude Phytase was partially purified with a protein recovery of 43%, revealing a molecular weight of 120 kDa. It had an enzyme kinetic value of Km 3.3 mM and a Vmax of 19.1 mol/min. The 3D structure of PhyS1 amino acid sequences (PhyS1. B99990002) was simulated using Modeler 9.23, and the validated result revealed that 86.7% were in the favored region by Ramachandran plot. The SAVES server verified the 3D PDB file as satisfactory, and the model (in.pdb format) was uploaded in the PMDB database with the accession number ID: PM0082974. At the lab level, Hanseniaspora guilliermondii S1 (MG663578) producing phytase exhibited successful plant growth promotion activity in Ragi - CO 19 (Eleusine coracana L.) and Rice -Navarai - IR 64 (Oryza sativa L.). As a result, a phytase-based formulation for sustainable agriculture must be developed and tested on a large scale in diverse geographical areas of agricultural lands to determine its effect and potential on plant development.
•SSF optimized via OVAT strategy and Box-Behnken design.•Protein model adequate for phytase production (91% accuracy).•Phytase productivity highest with jackfruit seed powder substrate.•Prediction of active sites and 3D model of Phytase from H. guilliermondii S1.•H. guilliermondii S1 (MG663578) phytase promotes Rice plant growth.
Antibodies developed for research and clinical applications may exhibit suboptimal stability, expressibility, or affinity. Existing optimization strategies focus on surface mutations, whereas natural ...affinity maturation also introduces mutations in the antibody core, simultaneously improving stability and affinity. To systematically map the mutational tolerance of an antibody variable fragment (Fv), we performed yeast display and applied deep mutational scanning to an anti-lysozyme antibody and found that many of the affinity-enhancing mutations clustered at the variable light-heavy chain interface, within the antibody core. Rosetta design combined enhancing mutations, yielding a variant with tenfold higher affinity and substantially improved stability. To make this approach broadly accessible, we developed AbLIFT, an automated web server that designs multipoint core mutations to improve contacts between specific Fv light and heavy chains (http://AbLIFT.weizmann.ac.il). We applied AbLIFT to two unrelated antibodies targeting the human antigens VEGF and QSOX1. Strikingly, the designs improved stability, affinity, and expression yields. The results provide proof-of-principle for bypassing laborious cycles of antibody engineering through automated computational affinity and stability design.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Electricity cost is becoming a major portion of Internet data center (IDC)'s operation cost and large-scale IDCs are becoming important consumers of regional electricity markets. IDC's energy ...efficiency is gaining more attention by data center operators and electricity market operators. Effective IDC electric demand management solutions are eagerly sought by all stakeholders. In this paper, a mixed-integer programming model based IDC electric demand management solution is proposed, which integrates both the impacts of locational marginal electricity prices and power management capability of IDC itself. Dynamic voltage/frequency scaling of individual server, cluster server ON/OFF scheduling, and dynamic workload dispatching are optimized while complying with all the IDC system-wide and individual heterogeneous servers' operation constraints according to the IDC applications' temporal variant workload. Reduced electricity cost can be achieved together with guaranteed QoS requirement and reliability consideration by using the proposed model. World Cup '98 data is utilized to evaluate the effectiveness of the proposed solution. According to the experimental evaluation, electricity cost could be cut by more than 20% in a peak workload period and by more than 80% in a light workload period. Besides, more than 6% electricity cost could be cut by considering the impact of electricity price difference. Experimental results also reveal that higher QoS requirement and reliability consideration could result in higher electricity cost.
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