Structuprint: a scalable and extensible tool for two-dimensional representation of protein surfaces

© 2016 Kontopoulos et al.Background: The term molecular cartography encompasses a family of computational methods for two-dimensional transformation of protein structures and analysis of their physicochemical properties. The underlying algorithms comprise multiple manual steps, whereas the few existing implementations typically restrict the user to a very limited set of molecular descriptors. Results: We present Structuprint, a free standalone software that fully automates the rendering of protein surface maps, given - at the very least - a directory with a PDB file and an amino acid property. The tool comes with a default database of 328 descriptors, which can be extended or substituted by user-provided ones. The core algorithm comprises the generation of a mould of the protein surface, which is subsequently converted to a sphere and mapped to two dimensions, using the Miller cylindrical projection. Structuprint is partly optimized for multicore computers, making the rendering of animations of entire molecular dynamics simulations feasible. Conclusions: Structuprint is an efficient application, implementing a molecular cartography algorithm for protein surfaces. According to the results of a benchmark, its memory requirements and execution time are reasonable, allowing it to run even on low-end personal computers. We believe that it will be of use - primarily but not exclusively - to structural biologists and computational biochemists

Protein signatures using electrostatic molecular surfaces in harmonic space

We developed a novel method based on the Fourier analysis of protein molecular surfaces to speed up the analysis of the vast structural data generated in the post-genomic era. This method computes the power spectrum of surfaces of the molecular electrostatic potential, whose three-dimensional coordinates have been either experimentally or theoretically determined. Thus we achieve a reduction of the initial three-dimensional information on the molecular surface to the one-dimensional information on pairs of points at a fixed scale apart. Consequently, the similarity search in our method is computationally less demanding and significantly faster than shape comparison methods. As proof of principle, we applied our method to a training set of viral proteins that are involved in major diseases such as Hepatitis C, Dengue fever, Yellow fever, Bovine viral diarrhea and West Nile fever. The training set contains proteins of four different protein families, as well as a mammalian representative enzyme. We found that the power spectrum successfully assigns a unique signature to each protein included in our training set, thus providing a direct probe of functional similarity among proteins. The results agree with established biological data from conventional structural biochemistry analyses.Comment: 9 pages, 10 figures Published in PeerJ (2013), https://peerj.com/articles/185

Μέθοδοι και εργαλεία για την υποστήριξη της επιχειρησιακής διαχείρισης του κινδύνου ξηρασίας σε περιοχές με υδατικές πιέσεις

The overall scope of the research is to develop operational methods and tools for supporting drought risk management in water stressed areas. It aims at linking science to the decision and policy-making process and providing supportive engineering tools. It proposes a holistic methodology based on the basic concepts of mainstreaming and proactive drought risk management, implementing a step-wise approach. Europe has experienced in the past 40 years drought episodes of various severities, with adverse impacts on the environment and the society. Policy actions have been intensified in order to increase the resilience of the affected regions. In this direction, the current research proposes a generic process for DRM mainstreaming, building around four basic steps: Definition of a Drought Risk ProfileIdentify DRM options: design and simulation of mitigation measuresPrioritize DRM options: Optimization and Decision-makingInternalize DRM: Definition of policy targets and ImplementationAcross these four steps, the following tools and methods have been developed:A methodology to map Drought Hazard, based on operational precipitation-derived indicators. A new drought indicator (DHI) has been developed A methodology for the characterization and mapping of Drought Vulnerability. A new drought indicator (DVI) has been developed, which is based on the balance between water resources availability and demandA methodology for developing a Drought Risk Profile (DRP) by overlaying the hazard and vulnerability componentsA generic methodology for designing Demand Management Options (i.e. interventions and measures covering management, technological and economic aspects) for the urban and agricultural sectors, incorporating the development of “cost-effective intervention curves”A methodology for linking interventions to the decision-making process. A Decision Support System (DSS) has been developed, consisting of three components: the WEAP21 (simulation engine), MATLAB (optimization engine), the intervention curves (library of measures)Practical recommendations on internalizing DRM. A methodology for testing the robustness of the optimization results under future climate and socio-economic scenarios has been defined. Practical suggestions on how to define policy targets and how to implement a process for integrating them into development frameworks are drafted.The proposed methodology and tools have been evaluated in the Ali-Efenti River Basin in Greece.Αντικείμενο της Δ.Δ. είναι η ανάπτυξη επιχειρησιακών μεθόδων και εργαλείων για την υποστήριξη της διαχείρισης του κινδύνου ξηρασίας (ΔΚΞ) σε περιοχές υδατικές πιέσεις. Η έρευνα στοχεύει στη διασύνδεση της επιστήμης με τη διαδικασία λήψης αποφάσεων, και την παροχή υποστηρικτικών εργαλείων. Προτείνει μια ολιστική μέθοδο που στηρίζεται στις βασικές έννοιες της «ενσωμάτωσης” και της προληπτικής ΔΚΞ. Τα τελευταία 40 χρόνια η Ευρώπη έχει βιώσει επεισόδια ξηρασίας ποικίλης βαρύτητας. Οι δράσεις πολιτικής έχουν ενταθεί ώστε να αυξηθεί η προσαρμοστικότητα των πληγεισών περιοχών. Στην κατεύθυνση αυτή, η παρούσα έρευνα προτείνει μια γενικευμένη διαδικασία για την ενσωμάτωση της ΔΚΞ, βασισμένη σε τέσσερα κύρια βήματα:Ορισμός και ανάπτυξη Προφίλ Κινδύνου Ξηρασίας Προσδιορισμός παρεμβάσεων για τη ΔΚΞ: σχεδιασμός και προσομοίωση μέτρων μετριασμού. Ιεράρχηση των παρεμβάσεων και καθορισμός προτεραιοτήτων: Βελτιστοποίηση και λήψη αποφάσεων. Ενσωμάτωση της ΔΚΞ: Ορισμός στόχων πολιτικής και εφαρμογή Για την υποστήριξη και πρακτική εφαρμογή αυτών των βημάτων αναπτύχθηκαν οι ακόλουθες μέθοδοι/εργαλεία:Μεθοδολογία για την χαρτογράφηση της Επικινδυνότητας Ξηρασίας, βάση επιχειρησιακών δεικτών, και ανάπτυξη ενός νέου Δείκτης Επικινδυνότητας Ξηρασίας (DHI) Μεθοδολογία για τη χαρτογράφηση της Τρωτότητας στην Ξηρασία, και ανάπτυξη ενός νέου Δείκτη Τρωτότητας Ξηρασίας (DVI)Μεθοδολογία για την ανάπτυξη Προφίλ Κινδύνου Ξηρασίας, με υπέρθεση της επικινδυνότητας και τρωτότητας Γενικευμένη μεθοδολογία για τον σχεδιασμό Μέτρων Διαχείρισης της Ζήτησης (δηλ. παρεμβάσεων που καλύπτουν διαχειριστικές, τεχνολογικές, οικονομικές πτυχές) για τον αστικό και αγροτικό τομέα, ενσωματώνοντας την ανάπτυξη «καμπύλων παρέμβασης» κόστους-οφέλους. Μεθοδολογία διασύνδεσης μέτρων με τη διαδικασία λήψης αποφάσεων. Αναπτύχθηκε ένα Σύστημα Υποστήριξης Αποφάσεων (ΣΥΑ) που αποτελείται από τρεις συνιστώσες: το WEAP21 (μηχανή προσομοίωσης), το MATLAB (μηχανή βελτιστοποίησης), τις καμπύλες παρέμβασης (βιβλιοθήκη μέτρων), και στοχεύει στην επιλογή της βέλτιστης δέσμης μέτρων διαχείρισης και στόχων πολιτικής. Πρακτικές συστάσεις για την ενσωμάτωση της ΔΚΞ. Καθορίστηκε μια μεθοδολογία για τον έλεγχο της ευρωστίας των αποτελεσμάτων βελτιστοποίησης υπό συνθήκες μελλοντικών κλιματικών και κοινωνικό-οικονομικών σεναρίων. Συντάχθηκαν προτάσεις για τον καθορισμό στόχων πολιτικής και την ενσωμάτωσή τους σε αναπτυξιακά πλαίσια.Η προτεινόμενη μεθοδολογία και τα εργαλεία αξιολογήθηκαν λεκάνη Αλή-Εφέντη στην Ελλάδα

Cytosine Methyltransferases as Tumor Markers

Changes in DNA methylation patterns is a prominent characteristic of human tumors. Tumor cells display reduced levels of genomic DNA methylation and site-specific CpG island hypermethylation. Methylation of CpG dinucleotides is catalyzed by the enzyme family of DNA methyltransferases (DNMTs). In this review, the role of DNA methylation and DNMTs as key determinants of carcinogenesis is further elucidated. The chromatin modifying proteins that are known to interact with DNMTs are also described. Finally, the role of DNMTs as potential therapeutic targets is addressed

AmalgamScope: merging annotations data across the human genome

The past years have shown an enormous advancement in sequencing and array-based technologies, producing supplementary or alternative views of the genome stored in various formats and databases. Their sheer volume and different data scope pose a challenge to jointly visualize and integrate diverse data types. We present AmalgamScope a new interactive software tool focusing on assisting scientists with the annotation of the human genome and particularly the integration of the annotation files from multiple data types, using gene identifiers and genomic coordinates. Supported platforms include next-generation sequencing and microarray technologies. The available features of AmalgamScope range from the annotation of diverse data types across the human genome to integration of the data based on the annotational information and visualization of the merged files within chromosomal regions or the whole genome. Additionally, users can define custom transcriptome library files for any species and use the file exchanging distant server options of the tool

Space constrained homology modelling: The paradigm of the RNA-dependent RNA polymerase of dengue (Type II) virus

Protein structure is more conserved than sequence in nature. In this direction we developed a novel methodology that significantly improves conventional homology modelling when sequence identity is low, by taking into consideration 3D structural features of the template, such as size and shape. Herein, our new homology modelling approach was applied to the homology modelling of the RNA-dependent RNA polymerase (RdRp) of dengue (type II) virus. The RdRp of dengue was chosen due to the low sequence similarity shared between the dengue virus polymerase and the available templates, while purposely avoiding to use the actual X-ray structure that is available for the dengue RdRp. The novel approach takes advantage of 3D space corresponding to protein shape and size by creating a 3D scaffold of the template structure. The dengue polymerase model built by the novel approach exhibited all features of RNA-dependent RNA polymerases and was almost identical to the X-ray structure of the dengue RdRp, as opposed to the model built by conventional homology modelling. Therefore, we propose that the space-aided homology modelling approach can be of a more general use to homology modelling of enzymes sharing low sequence similarity with the template structures. © 2013 Dimitrios Vlachakis et al

Insights into the structure and 3D spatial arrangement of the b-ketoacyl carrier protein synthases

The b-ketoacyl carrier protein synthases (the KAS enzymes) are key enzymes that can be used as potential anti-Plasmodium drug targets. In bacteria, three KAS enzymes have been identified (KAS I, KAS II and KAS III), whilst in Plasmodium a KAS I/II and KAS III enzyme has been reported. The protein has a total of four active sites, which have been found to be different to each other, rather than four copies of the same active site. The active sites differ not only in the type of interaction they establish with the ligand, but, in the case of Cerulenin as a ligand, the active sites of the KAS I/II enzyme also differ in the number of residues involved in the ligand protein interaction. This is very interesting biochemically, because these differences imply that the affinity of each active site for binding to the ligand might be different as well.