scholarly journals Exploring ion channel mechanisms : from toxin-based tools to computational methods

2016 ◽  
Author(s):  
◽  
Autoosa Salari
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Building Blocks ◽  
Proper Function ◽  
Computational Techniques ◽  
Pharmacological Agents ◽  
Cellular Excitability ◽  
Basic Functions ◽  
Five Senses ◽  
First Time

Ion channels are the building blocks of cellular excitability, controlling the most basic functions necessary for life to the most complex behaviors. The research presented here addresses questions about the mechanisms by which different ion channels function, as well as, how various toxins from venomous animals can alter ion channel behavior. This was done using a combination of molecular biology, electrophysiology, and computational techniques. The results shed light on the specific structures of a channel required for proper function, and target by pharmacological agents. Importantly, these results have significance in developing animal toxins as research tools and as future therapeutic agents for ion channel associated diseases. Lastly, we demonstrate for the first time, a system to study a protein required for high temperature avoidance in fruit flies. This opens the door to addressing detailed questions about the most poorly understood of the five senses, temperature sensation.

scholarly journals Computational Methods of Studying the Binding of Toxins From Venomous Animals to Biological Ion Channels: Theory and Applications

2013 ◽  
Vol 93 (2) ◽  
pp. 767-802 ◽  
Author(s):  
Dan Gordon ◽  
Rong Chen ◽  
Shin-Ho Chung
Keyword(s):  
Ion Channels ◽  
Computational Modeling ◽  
Ion Channel ◽  
Computational Methods ◽  
Structural Information ◽  
Structural Features ◽  
New Drugs ◽  
Computational Techniques ◽  
Theoretical Understanding ◽  
Theoretical Concepts

The discovery of new drugs that selectively block or modulate ion channels has great potential to provide new treatments for a host of conditions. One promising avenue revolves around modifying or mimicking certain naturally occurring ion channel modulator toxins. This strategy appears to offer the prospect of designing drugs that are both potent and specific. The use of computational modeling is crucial to this endeavor, as it has the potential to provide lower cost alternatives for exploring the effects of new compounds on ion channels. In addition, computational modeling can provide structural information and theoretical understanding that is not easily derivable from experimental results. In this review, we look at the theory and computational methods that are applicable to the study of ion channel modulators. The first section provides an introduction to various theoretical concepts, including force-fields and the statistical mechanics of binding. We then look at various computational techniques available to the researcher, including molecular dynamics, Brownian dynamics, and molecular docking systems. The latter section of the review explores applications of these techniques, concentrating on pore blocker and gating modifier toxins of potassium and sodium channels. After first discussing the structural features of these channels, and their modes of block, we provide an in-depth review of past computational work that has been carried out. Finally, we discuss prospects for future developments in the field.

scholarly journals Perspective of Ion Channels in Prostate Cancer

2021 ◽  
pp. 69-72
Author(s):  
Nnodim Johnkennedy ◽  
Bako Hauwa ◽  
Ezekwesiri Cletus
Keyword(s):  
Prostate Cancer ◽  
Ion Channels ◽  
Membrane Proteins ◽  
Ion Channel ◽  
Prostate Cancer Cell ◽  
Ionic Homeostasis ◽  
Tissue Invasion ◽  
Cellular Excitability ◽  
Genes Encoding ◽  
Inherited Mutations

Ion channels are membrane proteins, which play a great role in regulating cellular excitability. Alteration of ion channel may contribute to prostate cancer. This could be linked to inherited mutations of ion channel genes which alter channel’s biophysical properties, in a prostate cancer. It is an observed fact that genomic instability is the main cause as well as the major characteristics of prostate cancer. Prostate cancer cell genotypes are mainly characterized by uncontrolled metastasis, resistance to programmed cell death, sustained angiogenesis as well as tissue invasion and metastasis. It is known that genes encoding ion channels are affected in prostate cancer. The Membrane proteins which is involved in signaling in cell and among cells, for coupling of extracellular events with intracellular responses, and for maintaining intracellular ionic homeostasis ion channels which contribute to some extents to pathophysiological features of each prostate cancer.

scholarly journals ICGenealogy: Mapping the Function of Neuronal Ion Channels in Model and Experiment

2016 ◽  
Author(s):  
William F Podlaski ◽  
Alexander Seeholzer ◽  
Lukas N Groschner ◽  
Gero Miesenböck ◽  
Rajnish Ranjan ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Large Scale ◽  
Building Blocks ◽  
Web Interface ◽  
Neuron Models ◽  
Channel Models ◽  
Ion Channel Kinetics ◽  
Scale Classification

SummaryIon channel models are the building blocks of computational neuron models. Their biological fidelity is therefore crucial for the interpretability of simulations. However, the number of published models, and the lack of standardization, make the comparison of models with one another and with experimental data difficult. Here, we present a framework for the automated large-scale classification of ion channel models. Using annotated metadata and model responses to a set of voltage-clamp protocols, we assigned 2378 models of voltage- and calcium-gated ion channels coded in NEURON to 211 clusters. The IonChannelGenealogy web interface provides an interactive resource for the categorization of new and existing models and experimental recordings. It enables quantitative comparisons of simulated and/or measured ion channel kinetics, and facilitates field-wide standardization of experimentally-constrained modeling.

scholarly journals Perspective of Ion Channels in Prostate Cancer

2021 ◽  
pp. 72-75
Author(s):  
Nnodim Johnkennedy ◽  
Bako Hauwa ◽  
Ezekwesiri Cletus
Keyword(s):  
Prostate Cancer ◽  
Ion Channels ◽  
Membrane Proteins ◽  
Ion Channel ◽  
Prostate Cancer Cell ◽  
Ionic Homeostasis ◽  
Tissue Invasion ◽  
Cellular Excitability ◽  
Genes Encoding ◽  
Inherited Mutations

Ion channels are membrane proteins, which play a great role in regulating cellular excitability. Alteration of ion channel may contribute to prostate cancer. This could be linked to inherited mutations of ion channel genes which alter channel’s biophysical properties, in a prostate cancer. It is an observed fact that genomic instability is the main cause as well as the major characteristics of prostate cancer. Prostate cancer cell genotypes are mainly characterized by uncontrolled metastasis, resistance to programmed cell death, sustained angiogenesis as well as tissue invasion and metastasis. It is known that genes encoding ion channels are affected in prostate cancer. The Membrane proteins which is involved in signaling in cell and among cells, for coupling of extracellular events with intracellular responses, and for maintaining intracellular ionic homeostasis ion channels which contribute to some extents to pathophysiological features of each prostate cancer.

scholarly journals Mapping the function of neuronal ion channels in model and experiment

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
William F Podlaski ◽  
Alexander Seeholzer ◽  
Lukas N Groschner ◽  
Gero Miesenböck ◽  
Rajnish Ranjan ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Large Scale ◽  
Building Blocks ◽  
Web Interface ◽  
Neuron Models ◽  
Channel Models ◽  
Ion Channel Kinetics ◽  
Scale Classification

Ion channel models are the building blocks of computational neuron models. Their biological fidelity is therefore crucial for the interpretation of simulations. However, the number of published models, and the lack of standardization, make the comparison of ion channel models with one another and with experimental data difficult. Here, we present a framework for the automated large-scale classification of ion channel models. Using annotated metadata and responses to a set of voltage-clamp protocols, we assigned 2378 models of voltage- and calcium-gated ion channels coded in NEURON to 211 clusters. The IonChannelGenealogy (ICGenealogy) web interface provides an interactive resource for the categorization of new and existing models and experimental recordings. It enables quantitative comparisons of simulated and/or measured ion channel kinetics, and facilitates field-wide standardization of experimentally-constrained modeling.

Probing the Substrate Promiscuity of Isopentenyl Phosphate Kinase as a Platform for Hemiterpene Analogue Production

2019 ◽  
Author(s):  
Sean Lund ◽  
Taylor Courtney ◽  
Gavin Williams
Keyword(s):  
Synthetic Biology ◽  
Building Blocks ◽  
Isoprenoid Biosynthesis ◽  
Thermoplasma Acidophilum ◽  
Substrate Promiscuity ◽  
Enzymatic Pathways ◽  
First Time ◽  
Rate Limiting ◽  
Alcohol Dependent ◽  
Isopentenyl Phosphate

Isoprenoids are a large class of natural products with wide-ranging applications. Synthetic biology approaches to the manufacture of isoprenoids and their new-to-nature derivatives are limited due to the provision in Nature of just two hemiterpene building blocks for isoprenoid biosynthesis. To address this limitation, artificial chemo-enzymatic pathways such as the alcohol-dependent hemiterpene pathway (ADH) serve to leverage consecutive kinases to convert exogenous alcohols to pyrophosphates that could be coupled to downstream isoprenoid biosynthesis. To be successful, each kinase in this pathway should be permissive of a broad range of substrates. For the first time, we have probed the promiscuity of the second enzyme in the ADH pathway, isopentenyl phosphate kinase from Thermoplasma acidophilum, towards a broad range of acceptor monophosphates. Subsequently, we evaluate the suitability of this enzyme to provide non-natural pyrophosphates and provide a critical first step in characterizing the rate limiting steps in the artificial ADH pathway.<br>

scholarly journals A Sustainable Improvement of ω-Bromoalkylphosphonates Synthesis to Access Novel KuQuinones

Organics ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 107-117
Author(s):  
Mattia Forchetta ◽  
Valeria Conte ◽  
Giulia Fiorani ◽  
Pierluca Galloni ◽  
Federica Sabuzi
Keyword(s):  
Metal Oxides ◽  
Phosphonic Acid ◽  
Organic Molecules ◽  
Building Blocks ◽  
Reaction Conditions ◽  
Phosphonic Acids ◽  
Sustainable Improvement ◽  
Phosphonate Esters ◽  
First Time ◽  
Complex Organic

Owing to the attractiveness of organic phosphonic acids and esters in the pharmacological field and in the functionalization of conductive metal-oxides, the research of effective synthetic protocols is pivotal. Among the others, ω-bromoalkylphosphonates are gaining particular attention because they are useful building blocks for the tailored functionalization of complex organic molecules. Hence, in this work, the optimization of Michaelis–Arbuzov reaction conditions for ω-bromoalkylphosphonates has been performed, to improve process sustainability while maintaining good yields. Synthesized ω-bromoalkylphosphonates have been successfully adopted for the synthesis of new KuQuinone phosphonate esters and, by hydrolysis, phosphonic acid KuQuinone derivatives have been obtained for the first time. Considering the high affinity with metal-oxides, KuQuinones bearing phosphonic acid terminal groups are promising candidates for biomedical and photo(electro)chemical applications.

scholarly journals Bacterial cellulose spheroids as building blocks for 3D and patterned living materials and for regeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joaquin Caro-Astorga ◽  
Kenneth T. Walker ◽  
Natalia Herrera ◽  
Koon-Yang Lee ◽  
Tom Ellis
Keyword(s):  
Bacterial Cellulose ◽  
Building Blocks ◽  
Genetically Engineered ◽  
High Yield ◽  
Synthetic Materials ◽  
Chemical Inputs ◽  
First Time ◽  
3D Shapes ◽  
Promising Avenue ◽  
Living Materials

AbstractEngineered living materials (ELMs) based on bacterial cellulose (BC) offer a promising avenue for cheap-to-produce materials that can be programmed with genetically encoded functionalities. Here we explore how ELMs can be fabricated in a modular fashion from millimetre-scale biofilm spheroids grown from shaking cultures of Komagataeibacter rhaeticus. Here we define a reproducible protocol to produce BC spheroids with the high yield bacterial cellulose producer K. rhaeticus and demonstrate for the first time their potential for their use as building blocks to grow ELMs in 3D shapes. Using genetically engineered K. rhaeticus, we produce functionalized BC spheroids and use these to make and grow patterned BC-based ELMs that signal within a material and can sense and report on chemical inputs. We also investigate the use of BC spheroids as a method to regenerate damaged BC materials and as a way to fuse together smaller material sections of cellulose and synthetic materials into a larger piece. This work improves our understanding of BC spheroid formation and showcases their great potential for fabricating, patterning and repairing ELMs based on the promising biomaterial of bacterial cellulose.

scholarly journals Regulation of Cardiac Conduction and Arrhythmias by Ankyrin/Spectrin-Based Macromolecular Complexes

2021 ◽  
Vol 8 (5) ◽  
pp. 48
Author(s):  
Drew Nassal ◽  
Jane Yu ◽  
Dennison Min ◽  
Cemantha Lane ◽  
Rebecca Shaheen ◽  
...  
Keyword(s):  
Ion Channels ◽  
Cardiac Disease ◽  
Conduction System ◽  
Cytoskeletal Proteins ◽  
Cardiac Conduction ◽  
Proper Function ◽  
Cardiac Conduction System ◽  
Loss Of Function ◽  
Macromolecular Complexes ◽  
Conduction Disturbances

The cardiac conduction system is an extended network of excitable tissue tasked with generation and propagation of electrical impulses to signal coordinated contraction of the heart. The fidelity of this system depends on the proper spatio-temporal regulation of ion channels in myocytes throughout the conduction system. Importantly, inherited or acquired defects in a wide class of ion channels has been linked to dysfunction at various stages of the conduction system resulting in life-threatening cardiac arrhythmia. There is growing appreciation of the role that adapter and cytoskeletal proteins play in organizing ion channel macromolecular complexes critical for proper function of the cardiac conduction system. In particular, members of the ankyrin and spectrin families have emerged as important nodes for normal expression and regulation of ion channels in myocytes throughout the conduction system. Human variants impacting ankyrin/spectrin function give rise to a broad constellation of cardiac arrhythmias. Furthermore, chronic neurohumoral and biomechanical stress promotes ankyrin/spectrin loss of function that likely contributes to conduction disturbances in the setting of acquired cardiac disease. Collectively, this review seeks to bring attention to the significance of these cytoskeletal players and emphasize the potential therapeutic role they represent in a myriad of cardiac disease states.

On the generalized fractional Laplacian

2021 ◽  
Vol 24 (6) ◽  
pp. 1797-1830
Author(s):  
Chenkuan Li
Keyword(s):  
Fractional Laplacian ◽  
Special Functions ◽  
Computational Techniques ◽  
Residue Theorem ◽  
End Points ◽  
Proper Subspace ◽  
Classical Sense ◽  
First Time ◽  
Cauchy’S Residue Theorem ◽  
Integral Identities

Abstract The objective of this paper is, for the first time, to extend the fractional Laplacian (−△) s u(x) over the space Ck (Rn ) (which contains S(Rn ) as a proper subspace) for all s > 0 and s ≠ 1, 2, …, based on the normalization in distribution theory, Pizzetti’s formula and surface integrals in Rn . We further present two theorems showing that our extended fractional Laplacian is continuous at the end points 1, 2, … . Two illustrative examples are provided to demonstrate computational techniques for obtaining the fractional Laplacian using special functions, Cauchy’s residue theorem and integral identities. An application to defining the Riesz derivative in the classical sense at odd numbers is also considered at the end.

Sign in / Sign up

Export Citation Format

Share Document