Shelling the Voronoi interface of protein-protein complexes predicts residue activity and conservation

The accurate description of protein-protein interfaces remains a challenging task. Traditional criteria, based on atomic contacts or changes in solvent accessibility, tend to over or underpredict the interface itself and cannot discriminate active from less relevant parts. A recent simulation study by Mihalek and co-authors (2007, JMB 369, 584-95) concluded that active residues tend to be `dry', that is, insulated from water fluctuations. We show that patterns of `dry' residues can, to a large extent, be predicted by a fast, parameter-free and purely geometric analysis of protein interfaces. We introduce the shelling order of Voronoi facets as a straightforward quantitative measure of an atom's depth inside an interface. We analyze the correlation between Voronoi shelling order, dryness, and conservation on a set of 54 protein-protein complexes. Residues with high shelling order tend to be dry; evolutionary conservation also correlates with dryness and shelling order but, perhaps not surprisingly, is a much less accurate predictor of either property. Voronoi shelling order thus seems a meaningful and efficient descriptor of protein interfaces. Moreover, the strong correlation with dryness suggests that water dynamics within protein interfaces may, in first approximation, be described by simple diffusion models

Is coherence catalytic?

Quantum coherence, the ability to control the phases in superposition states is a resource, and it is of crucial importance, therefore, to understand how it is consumed in use. It has been suggested that catalytic coherence is possible, that is repeated use of the coherence without degradation or reduction in performance. The claim has particular relevance for quantum thermodynamics because, were it true, it would allow free energy that is locked in coherence to be extracted $\textit{indefinitely}$. We address this issue directly with a careful analysis of the proposal by $\AA{}$berg. We find that coherence $\textit{cannot}$ be used catalytically, or even repeatedly without limit.Comment: 23 pages with 2 figure

Metal Fluorides as Analogs for Studies on Phosphoryl Transfer Enzymes

The 1994 structure of a transition state analog with AlF4- and GDP complexed to G1, a small G protein, heralded a new field of research into structure and mechanism of enzymes that manipulate transfer of the phosphoryl (PO3-) group. The list of enzyme structures that embrace metal fluorides, MFx, as ligands that imitate either the phosphoryl group or a phosphate, is now growing at over 80 per triennium. They fall into three distinct geometrical classes: (i) Tetrahedral complexes, based on BeF3-, mimic ground state phosphates; (ii) Octahedral complexes, primarily based on AlF4-, mimic "in-line" anionic transition state for phosphoryl transfer; and (iii) Trigonal bipyramidal complexes, represented by MgF3- and putative AlF30 moieties, additionally mimic the tbp geometry of the transition state. The interpretation of these structures provides a deeper mechanistic understanding of the behavior and manipulation of phosphate monoesters in molecular biology. This review provides a comprehensive overview of these structures, their uses, and their computational development. It questions the identification of AlF30 and MgF4= as tbp species in protein complexes and discusses the relevance of physical organic chemistry and water-based model studies for understanding phosphoryl group transfer in enzymes. It describes two roles for amino acid side-chains that mediate proton transfers during phosphoryl transfer, based on the analysis of protein/MFx structures. First, they deploy hydrogen bonding to neutral oxygen nucleophiles so as to orientate them for correct orbital overlap with the electrophilic phosphorus center. Secondly, they behave as classical general acid/base catalysts

26. Theorietag Automaten und Formale Sprachen 23. Jahrestagung Logik in der Informatik: Tagungsband

Der Theorietag ist die Jahrestagung der Fachgruppe Automaten und Formale Sprachen der Gesellschaft für Informatik und fand erstmals 1991 in Magdeburg statt. Seit dem Jahr 1996 wird der Theorietag von einem eintägigen Workshop mit eingeladenen Vorträgen begleitet. Die Jahrestagung der Fachgruppe Logik in der Informatik der Gesellschaft für Informatik fand erstmals 1993 in Leipzig statt. Im Laufe beider Jahrestagungen finden auch die jährliche Fachgruppensitzungen statt. In diesem Jahr wird der Theorietag der Fachgruppe Automaten und Formale Sprachen erstmalig zusammen mit der Jahrestagung der Fachgruppe Logik in der Informatik abgehalten. Organisiert wurde die gemeinsame Veranstaltung von der Arbeitsgruppe Zuverlässige Systeme des Instituts für Informatik an der Christian-Albrechts-Universität Kiel vom 4. bis 7. Oktober im Tagungshotel Tannenfelde bei Neumünster. Während des Tre↵ens wird ein Workshop für alle Interessierten statt finden. In Tannenfelde werden • Christoph Löding (Aachen) • Tomás Masopust (Dresden) • Henning Schnoor (Kiel) • Nicole Schweikardt (Berlin) • Georg Zetzsche (Paris) eingeladene Vorträge zu ihrer aktuellen Arbeit halten. Darüber hinaus werden 26 Vorträge von Teilnehmern und Teilnehmerinnen gehalten, 17 auf dem Theorietag Automaten und formale Sprachen und neun auf der Jahrestagung Logik in der Informatik. Der vorliegende Band enthält Kurzfassungen aller Beiträge. Wir danken der Gesellschaft für Informatik, der Christian-Albrechts-Universität zu Kiel und dem Tagungshotel Tannenfelde für die Unterstützung dieses Theorietags. Ein besonderer Dank geht an das Organisationsteam: Maike Bradler, Philipp Sieweck, Joel Day. Kiel, Oktober 2016 Florin Manea, Dirk Nowotka und Thomas Wilk

Design Environments for Complex Systems

The paper describes an approach for modeling complex systems by hiding as much formal details as possible from the user, still allowing verification and simulation of the model. The interface is based on UML to make the environment available to the largest audience. To carry out analysis, verification and simulation we automatically extract process algebras specifications from UML models. The results of the analysis is then reflected back in the UML model by annotating diagrams. The formal model includes stochastic information to handle quantitative parameters. We present here the stochastic -calculus and we discuss the implementation of its probabilistic support that allows simulation of processes. We exploit the benefits of our approach in two applicative domains: global computing and systems biology

Balancing Selection at the Tomato RCR3 Guardee Gene Family Maintains Variation in Strength of Pathogen Defense

Coevolution between hosts and pathogens is thought to occur between interacting molecules of both species. This results in the maintenance of genetic diversity at pathogen antigens (or so-called effectors) and host resistance genes such as the major histocompatibility complex (MHC) in mammals or resistance (R) genes in plants. In plant-pathogen interactions, the current paradigm posits that a specific defense response is activated upon recognition of pathogen effectors via interaction with their corresponding R proteins. According to the''Guard-Hypothesis,'' R proteins (the ``guards'') can sense modification of target molecules in the host (the ``guardees'') by pathogen effectors and subsequently trigger the defense response. Multiple studies have reported high genetic diversity at R genes maintained by balancing selection. In contrast, little is known about the evolutionary mechanisms shaping the guardee, which may be subject to contrasting evolutionary forces. Here we show that the evolution of the guardee RCR3 is characterized by gene duplication, frequent gene conversion, and balancing selection in the wild tomato species Solanum peruvianum. Investigating the functional characteristics of 54 natural variants through in vitro and in planta assays, we detected differences in recognition of the pathogen effector through interaction with the guardee, as well as substantial variation in the strength of the defense response. This variation is maintained by balancing selection at each copy of the RCR3 gene. Our analyses pinpoint three amino acid polymorphisms with key functional consequences for the coevolution between the guardee (RCR3) and its guard (Cf-2). We conclude that, in addition to coevolution at the ``guardee-effector'' interface for pathogen recognition, natural selection acts on the ``guard-guardee'' interface. Guardee evolution may be governed by a counterbalance between improved activation in the presence and prevention of auto-immune responses in the absence of the corresponding pathogen

Kaemika app, Integrating protocols and chemical simulation

Kaemika is an app available on the four major app stores. It provides deterministic and stochastic simulation, supporting natural chemical notation enhanced with recursive and conditional generation of chemical reaction networks. It has a liquid-handling protocol sublanguage compiled to a virtual digital microfluidic device. Chemical and microfluidic simulations can be interleaved for full experimental-cycle modeling. A novel and unambiguous representation of directed multigraphs is used to lay out chemical reaction networks in graphical form