scholarly journals Computational studies of protein–protein dissociation by statistical potential and coarse-grained simulations: a case study on interactions between colicin E9 endonuclease and immunity proteins

2019 ◽  
Vol 21 (5) ◽  
pp. 2463-2471 ◽  
Author(s):  
Zhaoqian Su ◽  
Yinghao Wu
Keyword(s):  
Protein Complexes ◽  
Simulation Method ◽  
Coarse Grained ◽  
Computational Studies ◽  
Knowledge Based ◽  
Protein Dissociation ◽  
Coarse Grained Simulations ◽  
Dissociation Mechanisms ◽  
Colicin E9

A coarse-grained simulation method and a knowledge-based potential were developed to explore the dissociation mechanisms of protein complexes.

scholarly journals Identification of critical residues in the colicin E9 DNase binding region of the Im9 protein

1997 ◽  
Vol 323 (3) ◽  
pp. 823-831 ◽  
Author(s):  
Michael J. OSBORNE ◽  
Russell WALLIS ◽  
Kit-Yi LEUNG ◽  
Glyn WILLIAMS ◽  
Lu-Yun LIAN ◽  
...  
Keyword(s):  
Binding Site ◽  
Protein Complexes ◽  
Dissociation Rate ◽  
15N Nmr ◽  
Binding Region ◽  
Nmr Studies ◽  
Immunity Protein ◽  
Wide Range ◽  
Protein Dissociation ◽  
Colicin E9

1H–15N NMR studies, in conjunction with mutagenesis experiments, have been used to delineate the DNase-binding surface of the colicin E9 inhibitor protein Im9 (where Im stands for immunity protein). Complexes were formed between the 15 kDa unlabelled E9 DNase domain and the 9.5 kDa Im9 protein uniformly labelled with 15N. Approx. 90% of the amide resonances of the bound Im9 were assigned and spectral parameters obtained from 1H–15N heteronuclear single quantum coherence (HSQC) spectra were compared with those for the free Im9 assigned previously. Many of the amide resonances were shifted on complex formation, some by more than 2 p.p.m. in the 15N dimension and more than 0.5 p.p.m. in the 1H dimension. Most of the strongly shifted amides are located on the surfaces of two of the four helices, helix II and helix III. Whereas helix II had already been identified through genetic and biochemical investigations as an important determinant of biological specificity, helix III had not previously been implicated in binding to the DNase. To test the robustness of the NMR-delineated DNase-binding site, a selection of Im9 alanine mutants were constructed and their dissociation rate constants from E9 DNase-immunity protein complexes quantified by radioactive subunit exchange kinetics. Their off-rates correlated well with the NMR perturbation analysis; for example, residues that were highly perturbed in HSQC experiments, such as residues 34 (helix II) and 54 (helix III), had a marked effect on the DNase–immunity protein dissociation rate when replaced by alanine. The NMR and mutagenesis data are consistent with a DNase-binding region on Im9 composed of invariant residues in helix III and variable residues in helix II. The relationship of this binding site model to the wide range of affinities (Kd values in the range 10-4 to 10-16 M) that have been measured for cognate and non-cognate colicin DNase–immunity protein interactions is discussed.

scholarly journals Using Coarse-Grained Simulations to Characterize the Mechanisms of Protein–Protein Association

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1056 ◽  
Author(s):  
Kalyani Dhusia ◽  
Zhaoqian Su ◽  
Yinghao Wu
Keyword(s):  
Protein Complex ◽  
Large Scale ◽  
Protein Complexes ◽  
Kinetic Property ◽  
Simulation Method ◽  
Coarse Grained ◽  
Structural Level ◽  
Simulation Approach ◽  
Protein Association ◽  
Order Of Magnitude

The formation of functionally versatile protein complexes underlies almost every biological process. The estimation of how fast these complexes can be formed has broad implications for unravelling the mechanism of biomolecular recognition. This kinetic property is traditionally quantified by association rates, which can be measured through various experimental techniques. To complement these time-consuming and labor-intensive approaches, we developed a coarse-grained simulation approach to study the physical processes of protein–protein association. We systematically calibrated our simulation method against a large-scale benchmark set. By combining a physics-based force field with a statistically-derived potential in the simulation, we found that the association rates of more than 80% of protein complexes can be correctly predicted within one order of magnitude relative to their experimental measurements. We further showed that a mixture of force fields derived from complementary sources was able to describe the process of protein–protein association with mechanistic details. For instance, we show that association of a protein complex contains multiple steps in which proteins continuously search their local binding orientations and form non-native-like intermediates through repeated dissociation and re-association. Moreover, with an ensemble of loosely bound encounter complexes observed around their native conformation, we suggest that the transition states of protein–protein association could be highly diverse on the structural level. Our study also supports the idea in which the association of a protein complex is driven by a “funnel-like” energy landscape. In summary, these results shed light on our understanding of how protein–protein recognition is kinetically modulated, and our coarse-grained simulation approach can serve as a useful addition to the existing experimental approaches that measure protein–protein association rates.

scholarly journals Extension of the Unres Package for Physics-Based Coarse-Grained Simulations of Proteins and Protein Complexes to Very Large Systems

2021 ◽  
Vol 120 (3) ◽  
pp. 83a-84a
Author(s):  
Adam K. Sieradzan ◽  
Cezary R. Czaplewski ◽  
Emilia A. Lubecka ◽  
Agnieszka G. Lipska ◽  
Agnieszka S. Karczynska ◽  
...  
Keyword(s):  
Protein Complexes ◽  
Coarse Grained ◽  
Large Systems ◽  
Coarse Grained Simulations

Cyberphysical Design Automation Framework for Knowledge-based Engineering

2013 ◽  
Vol 1 (1) ◽  
pp. 158-178
Author(s):  
Urcun John Tanik
Keyword(s):  
System Design ◽  
Design Process ◽  
Design Automation ◽  
Design Theory ◽  
Knowledge Bases ◽  
Knowledge Based ◽  
Knowledge Based Engineering ◽  
Cyberphysical System ◽  
Automation Framework

Cyberphysical system design automation utilizing knowledge based engineering techniques with globally networked knowledge bases can tremendously improve the design process for emerging systems. Our goal is to develop a comprehensive architectural framework to improve the design process for cyberphysical systems (CPS) and implement a case study with Axiomatic Design Solutions Inc. to develop next generation toolsets utilizing knowledge-based engineering (KBE) systems adapted to multiple domains in the field of CPS design automation. The Cyberphysical System Design Automation Framework (CPSDAF) will be based on advances in CPS design theory based on current research and knowledge collected from global sources automatically via Semantic Web Services. A case study utilizing STEM students is discussed.

Grand-Reaction Method for Simulations of Ionization Equilibria and Ion Partitioning in a Broad Range of pH and Ionic Strength

2019 ◽  
Author(s):  
Jonas Landsgesell ◽  
Oleg Rud ◽  
Pascal Hebbeker ◽  
Raju Lunkad ◽  
Peter Košovan ◽  
...  
Keyword(s):  
Mean Field ◽  
Coarse Grained ◽  
Reactive System ◽  
Acid Base ◽  
Buffer Solution ◽  
Reaction Method ◽  
Ionization Equilibria ◽  
Coarse Grained Simulations ◽  
Ph Range ◽  
Weak Polyelectrolytes

We introduce the grand-reaction method for coarse-grained simulations of acid-base equilibria in a system coupled to a reservoir at a given pH and concentration of added salt. It can be viewed as an extension of the constant-pH method and the reaction ensemble, combining explicit simulations of reactions within the system, and grand-canonical exchange of particles with the reservoir. Unlike the previously introduced methods, the grand-reaction method is applicable to acid-base equilibria in the whole pH range because it avoids known artifacts. However, the method is more general, and can be used for simulations of any reactive system coupled to a reservoir of a known composition. To demonstrate the advantages of the grand-reaction method, we simulated a model system: A solution of weak polyelectrolytes in equilibrium with a buffer solution. By carefully accounting for the exchange of all constituents, the method ensures that all chemical potentials are equal in the system and in the multi-component reservoir. Thus, the grand-reaction method is able to predict non-monotonic swelling of weak polyelectrolytes as a function of pH, that has been known from mean-field predictions and from experiments but has never been observed in coarse-grained simulations. Finally, we outline possible extensions and further generalizations of the method, and provide a set of guidelines to enable safe usage of the method by a broad community of users.<br><br>

scholarly journals Semantic and knowledge based support to business model evaluation to stimulate green behaviour of electric vehicles’ drivers and energy prosumers

2021 ◽  
Author(s):  
Beniamino Di Martino ◽  
Dario Branco ◽  
Luigi Colucci Cante ◽  
Salvatore Venticinque ◽  
Reinhard Scholten ◽  
...  
Keyword(s):  
Business Model ◽  
Model Evaluation ◽  
Business Models ◽  
Real Case ◽  
Sustainable Mobility ◽  
Semantic Framework ◽  
Knowledge Based ◽  
Survey Results ◽  
Energy Prosumers

AbstractThis paper proposes a semantic framework for Business Model evaluation and its application to a real case study in the context of smart energy and sustainable mobility. It presents an ontology based representation of an original business model and examples of inferential rules for knowledge extraction and automatic population of the ontology. The real case study belongs to the GreenCharge European Project, that in these last years is proposing some original business models to promote sustainable e-mobility plans. An original OWL Ontology contains all relevant Business Model concepts referring to GreenCharge’s domain, including a semantic description of TestCards, survey results and inferential rules.

scholarly journals First principles characterisation of bio–nano interface

2021 ◽  
Author(s):  
Ian Rouse ◽  
David Power ◽  
Erik G. Brandt ◽  
Matthew Schneemilch ◽  
Konstantinos Kotsis ◽  
...  
Keyword(s):  
Titanium Dioxide ◽  
First Principles ◽  
Computational Approach ◽  
Titania Nanoparticles ◽  
Coarse Grained ◽  
First Principles Study

We present a multiscale computational approach for the first-principles study of bio-nano interactions. Using titanium dioxide as a case study, we evaluate the affinity of titania nanoparticles to water and biomolecules through atomistic and coarse-grained techniques.

Knowledge transfer roles of subsidiaries in MNCs’ networks

2019 ◽  
Vol 29 (4) ◽  
pp. 329-346 ◽  
Author(s):  
Cigdem Baskici
Keyword(s):  
Knowledge Transfer ◽  
Single Case ◽  
Research Question ◽  
Hierarchical Structures ◽  
Knowledge Flows ◽  
Consumer Electronics ◽  
Knowledge Network ◽  
Content Type ◽  
Knowledge Based

Purpose Although there have been a considerable number of studies regarding subsidiary role typology in multinationals’ management literature, there appear to be few studies that consider knowledge-based role typology from the network-based perspective. The purpose of this study is to fill this gap and extend the study of Gupta and Govindarajan (1991). Thus, the study focuses on answering the following research question: Do subsidiaries have different roles in terms of knowledge flows within a multinational company (MNC)? Design/methodology/approach This empirical study has been carried out as an explorative single case study. An MNC with 15 foreign subsidiaries headquartered in Turkey, which operated in the manufacturing of household appliances and consumer electronics, has been selected as the case. Knowledge transfer is analyzed in this MNC from the network perspective. Findings Four role typologies are detected for subsidiaries of the MNC: collector transmitter, collector diffuser, converter transmitter and converter diffuser. Research limitations/implications Findings of this study are specific to this case. Testing the findings in a sample consisting of subsidiaries of MNCs producing transnational products may contribute to the generalizability of these roles. Practical implications This study offers potentially important findings for MNC managers to use. First, in this study, knowledge flows' route could be defined within MNCs’ dual network. Second, role typologies could inform MNC managers to design their MNCs’ knowledge network. Originality/value The suggested typologies are expected to more accurately define the roles of subsidiaries within contemporary MNCs which are accepted to be transformed from hierarchical structures to network-based organizations.

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