AJP	ISSN : 0971 – 3093 Vol 29, Nos 8 & 9, August-September, 2020

 

Vol. 23, No 5 (2014) 723-733

Interpenetration model for electrostatic interaction between two soft particles

 

Hiroyuki Ohshima

Faculty of Pharmaceutical Sciences, Tokyo University of Science

A theory of the electrostatic interaction between two interpenetrating soft particles (i.e., porous particles with no particle core) of various geometries, e.g., plate, sphere, and cylinder in an electrolyte solution is developed. We assume that the electrostatic interaction follows three stages. That is, (i) the electrical double layer interaction between two soft particles before their contact with each other, (ii) partial penetration, and (iii) full penetration, i.e., engulfing of one particle by the other. Approximate analytic expressions for the interaction energy between an infinitely thick soft plate and a soft sphere, an infinitely long soft cylinder, or a soft plate of finite thickness at each stage are derived on the basis of the linearized Poisson-Boltzmann equation for the electric potential within and around the interacting soft particles. © Anita Publications. All right reserved.

 Vol. 23, No. 5 (2014) 735-744

Ion binding to biological macromolecules

 

Marharyta Petukh* and Emil Alexov

Computational Biophysics and Bioinformatics Laboratory

Biological macromolecules carry out their functions in water and in the presence of ions. The ions can bind to the macromolecules either specifically or non-specifically, or can simply to be a part of the water phase providing physiological gradient across various membranes. This review outlines the differences between specific and non-specific ion binding in terms of the function and stability of the corresponding macromolecules. Furthermore, the experimental techniques to identify ion positions and computational methods to predict ion binding are reviewed and their advantages compared. It is indicated that specifically bound ions are relatively easier to be revealed while non-specifically associated ions are difficult to predict. In addition, the binding and the residential time of non-specifically bound ions are very much sensitive to the environmental factors in the cells, specifically to the local pH and ion concentration. Since these characteristics differ among the cellular compartments, the non-specific ion binding must be investigated with respect to the sub-cellular localization of the corresponding macromolecule. © Anita Publications. All rights reserved.
Keywords: ion binding, ion dependent reactions, biological macromolecules, electrostatics.

 Vol. 23, No 5 (2014) 745-756

Post-docking optimization of protein-ligand interactions involving water molecules

 

Dessislava Jereva¹, Tania Pencheva¹, David Lagorce^2,3, Dimitri Desvillechabrol^2,3,Ilza Pajeva¹, Maria A Miteva^2,3

¹Institute of Biophysics and Biomedical Engineering – Bulgarian Academy of Sciences,105 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria

²INSERM, UMR-S 973, MTi, 75013 Paris, France

Water is an important component in biological systems mediating the interactions of macromolecules with various partners. Water molecules accommodated in binding sites of proteins are of particular importance for drug design. Taking water molecules into account in computational approaches to drug design, however, is an extremely challenging task, especially for a large number of ligands usually used for structure-based virtual screening. We previously developed the approach AMMOS to improve the quality of protein-ligand interaction predictions for in silico screening by using molecular mechanics optimization of docked protein-ligand complexes. In this study, we included explicit water molecules mediating protein-ligand interactions in AMMOS molecular mechanics optimization. The impact of considering water molecules in the protein binding site during the minimization on prediction of the ligand binding modes and binding energies was assessed and reported here.© Anita Publications. All rights reserved.

Keywords: AMMOS, post-docking optimization, binding site, protein flexibility, protein-ligand interactions, water molecules

 Vol. 23, No 5 (2014) 757-775

Computational Modeling of Disease Related Missense Mutations in Recently Crystalized Human G-Protein Coupled Receptors

 

Justin R Bartanus^1,2, Ben T Nguyen^1,3, Courtney A Balcome¹, Christopher A Henry¹, and Ekaterina I Michonova-Alexova^1*

²Presently a PhD student at Baylor College of Medicine, Houston, TX 77030, USA

The class of the G-protein coupled receptors (GPCRs) includes several hundred seven-helix transmembrane domain receptors, related to multiple key functions of the human body. Because of their critical importance, GPCRs were the focal point of the 2012 Nobel Prize in Chemistry.Variations, known as single nucleotide polymorphisms (SNPs), located in the coding sections of the DNA, may result in amino acid substitutions in the respective coded proteins.  Such SNPs, called non-synonymous (nsSNPs), have been observed in people susceptible or resistant to specific diseases. We studied selected nsSNPs in several recently crystalized human GPCRs, including the Human Histamine H1 Receptor (HHR1), the Human CXC Chemokine 4 Receptor (CXCR4), the Human β₂ Adrenergic Receptor (ADRB2), and the Human µ-Opioid Receptor (MOR), in order to understand the impact of some naturally occurring disease-related nsSNPs in them. Using computational modeling and biophysical approaches, we investigate how each one of these variations interferes with GPCRs wild type signaling properties by comparing the mutated properties with the wild type in an attempt to identify the impact of potentially disease causing missense mutations. The wild type and the mutant forms were modeled on the basis of the recently determined crystal structures of the receptors. While in all studied cases the nsSNPs destabilize of receptors, the major impact is observed when the original amino acid residue changes its charge as a result of the mutation. This work is based on four undergraduate research projects, partially funded by SCICU Student Faculty Research Grants.© Anita Publications. All rights reserved.© Anita Publications. All rights reserved.

 Vol. 23, No 5 (2014) 777-782

Review of the currently available methods for the compression of genomic re-sequencing data

 

The development of high-throughput sequencing technologies with the faster speed and efficiency has resulted in a massive increase of sequencing projects due to the faster speed and lower level of effort required. This has led to an accumulation of a tremendous amount of sequencing data, with an emergent need for methods for storage and transfer. Storing this data in the traditional methods, while plausible, is inefficient in that it requires a very large amount of storage space for what is mostly repetitive or very similar data. This problem has instigated the development of various methods for compressing and storing genomic data. This paper details the currently available methods for the compression of genomic sequence data. One of the most promising methods has been through the use of reference sequences to which only the differences in a target sequence are encoded. © Anita Publications. All right reserved.

 Vol. 23, No 5 (2014) 783-788

A comparison for MTS assay of PC12 cells cultured on collagen type IV and poly-lysine

 

Gregory S Barrett¹, Donna R Weinbrenner^{1, 2}, and Diana B Ivankovic¹

¹Anderson University Center for Cancer Research, Anderson, SC

Some scientists question the use of rat tail collagen coatings on plates using the MTS assay suggesting that the absorbance readings from the spectrophotometer may not be accurate. This article addresses the challenge of determining whether coating 96 well, polystyrene cell culture plates with rat tail collagen or poly-lysine affects the reliability or precision of MTS cell viability assays. For proper cell adhesion and differentiation to occur, PC12 cells must be grown on sub-culture vessels that have been coated with an extracellular matrix (ECM). It is then plausible, and some scientific debate exists, on whether these coatings hinder proper light transmittance necessary for absorption readings to be taken from a spectrophotometer. Coated and non-coated plates were tested in comparable conditions to determine if these necessary ECM obstruct monochromatic light from plate readers. It was shown that coating plates with an ECM does not affect the efficacy of microplate spectrophotometric absorbance readers at an alpha of 0.05 (p= 0.09 to 0.80). We also tested if PC12 cells respond preferentially to one coating versus the other, and suggest that PC12 cells sub-cultured on rat tail collagen give higher metabolic activity readings using the MTS assay compared to cells sub-cultured on the poly-lysine coating at alpha of 0.05 (p = <0.001).© Anita Publications. All rights reserved.

 Vol. 23, No 5 (2014) 789-814

Influence of electric field on cell behavior. Electrotreatment of cells for biomedical applications

 

Rumiana D Tzoneva

Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences

Electric fields are present in all developing and regenerating animal tissues. During recent years, there has been growing research on the response of cells to the endogenous and exogenously applied electric field. This review discusses the role of endogenous and applied (exogenous) electric field mainly in stimulating tissue regeneration and in cancer treatment by describing: 1) the historical context of bioelectricity, 2) the fundamental principles of cell and tissue response to electric fields, 3) the cellular mechanisms for the effects of low and high electricfields on cell behavior, and 4) the perspectives of using new techniques and approaches for electric field application in tissue regeneration and cancer treatment. © Anita Publications. All rights reserved.

 Vol. 23, No 5 (2014) 815-832

Understanding signaling cues in mitochondrial pathway mediated hypoxia using discrete pulse models

 

Rooplekha C Mitra^1*, Martha Y. Suárez Villagrán¹, John H. Miller, Jr.¹

It is now well established that mitochondrial dysfunction contributes to a variety of disorders ranging from type 2 diabetes, tissue inflammation, cardiac ischemia and cancer¹. For cardiac malfunction, the mechanism of mitochondrial damage has been linked to the dysregulation of cellular ion metabolism followed by intracellular calcium accumulation. Thereby ion dynamics regulation and energetics of cardiac cells under physiological and pathological conditions will provide important insights about the underlying processes. Hypoxic signaling modulates oxidative phosphorylation pathways which in turn leads to energy depletion, accumulation of cytotoxic mediators and cellular apoptosis². Previously it has been demonstrated that complexes III and IV are predominantly affected by reperfusion injury. Recent studies have postulated that under oxygen limiting conditions mitochondria produce NO indicating significant crosstalk between reactive oxygen species (ROS) and reactive nitrogen species (RNS)³.

                In this work we couple the basic building blocks of mitochondrial complexes important for oxidative mechanisms to the key functional units of the two compartment ROS and RNS pathways. In the reduced model we first identify the critically important players which govern the coordination and connectivity of the constituents based on our analysis of a set of hypoxic genes and proteins. That information is utilized to construct a novel mathematical method to transform the signaling network into a coupled system of differential equations (ODE) and also qualitatively analyzed using a binary logic circuit design using logic gates, latches and flip flops⁴. The states denote regulatory activation and inhibition. The evolution of the states is modelled with discrete time models as finite state machines. Evolution of hypoxia in the ODE system is modulated by the peroxide and NO cross-talk mechanisms. The circuit model generates a complementary qualitative information and the models for ionic species is constructed as purely Boolean gates and integrated into the layout of the signaling cascade by feedback loops. Cellular responses are modulated from the interference of the circuit components. In the next stage the leakage in the circuitry is attributed to proton leakage which is propagated in pathway modulating ROS. The stuck open fault mechanism is mapped to ROS homeostasis in the hypoxia-induced mitochondrial autophagy. From a general perspective this study has a promise to become alternative viable model to generate design rules for biochemical pathways which may readily be amenable to very large scale integration (VLSI) process simulation.© Anita Publications. All rights reserved.

Vol. 23, No 5 (2014) 833-837

Diffraction of the light of the firefly by a grating

 

Upamanyu Sharma, Mridusmita Phukan, Mana Mohan Rabha, and Anurup Gohain Barua*

A control experiment is performed to study diffraction of the light from three species of fireflies: one Indian species Luciola praeusta and two Japanese species Luciola cruciata and Luciola lateralis. The firefly emits stable, continuous light a few minutes after it is made to inhale vapors of ethyl acetate. The diffraction pattern produced by a plane diffraction grating of this light shows that the central principal maximum is predominantly yellow. From the first order principal maximum onwards, green and red colored bands appear. With increasing orders, these bands become broader which appear to suppress the yellow band. This result suggests that the intense yellow region, as a matter of fact, is very narrow, and the firefly most probably emits coherent yellow-colored light.© Anita Publications. All rights reserved.

Total Refs : 20

Vol. 23, No 5 (2014) 839-847

Strain-Dependent Difference in Cortical Electroencephalogram and Clinical Manifestations of Seizures inKainate Model of Temporal Lobe Epilepsy

 

JanaTchekalarova¹ and Lidia Kortenska

A commonly used method of diagnosis epilepsy is an EEG or electroencephalogram, which measures the patient’s electrical activity along the scalp. In clinical practice, EEG refers to the recording of the brain’s spontaneous electrical activity over a determined period of time. Analysis of EEG recording mainly involve spectral content of EEG, that is, the type of neural oscillations that can be observed in EEG signals.The similarity in EEG spectral profiles betweentwo rat strains, spontaneously hypertensive rats (SHRs) and kainate (KA)-treated normotensive rats, was suggestedto involvecommon mechanismsin geneticallydetermined generation ofspecific forms of oscillations in humans modeling temporal lobe epilepsy (TLE). In the present study, weaimed to compare cortical electroencephalogram (EEG) and clinical seizures of SHRs and Wistar rats in KA model of TLE. The power spectrums of baseline and epileptic EEGs were also investigated. We found no significant difference in the dose of KA required to induce status epilepticus (SE) between the two strains. However, the frequency of spontaneous motor seizureswas higher in SHRs than in Wistar rats during the stable chronic epileptic phase. In SHRs, the baseline EEG and EEG during SE, the latent and chronic phase was characterized by dominatingtheta activity and increased delta activity, which was detected in Wistar rats only during SE and the chronic epileptic phase.In conclusion, our findings showed similarity in EEG spectral profiles inSHRs before and after KA-induced SE, which is in line with the detected more severe seizure activity in this strain than in Wistar rats during the stable chronic epileptic phase.© Anita Publications. All rights reserved.
Keywords: kainate model; EEG; spectral profile; spontaneously hypertensive rats;Wistar rats.

 Vol. 23, No 5 (2014) 849-857

Innovations in Resting-state fMRI and MEG

 

Peka Christova

Functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) are modern imaging techniques that rely on physical phenomena to record brain activity. Both methods are non-invasive and require sophisticated equipment and recording conditions. The biological phenomena upon which they are based are different: fMRI measures the Blood Oxygenation Level-Dependent (BOLD) level, which reflects local hemodynamic changes, whereas MEG directly measures integrated local synaptic activity. The superior temporal resolution of MEG allows the assessment of short temporal interaction between the brain regions. Such assessments can apply to healthy subjects and patients. On the other hand, the superior spatial resolution of fMRI allows the precise localization of brain structures with a detailed inside view of brain connectivity patterns. The resting-state recordings of BOLD and MEG signals were analyzed as time series of each voxel/sensor. To estimate the true correlations between them, the prewhitened time series, called innovations, were used. © Anita Publications. All rights reserved.