Search results for: binding energy

Authors: Ho-Wa Li, Sai-Wing Tsang

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The excitonic effect in organic semiconductors plays a key role in determining the electronic devices performance. Strong exciton binding energy has been regarded as the detrimental factor limiting the further improvement in organic photovoltaic cells. To the best of our knowledge, only limited reported can be found in measuring the exciton binding energy in organic photovoltaic materials. Conventional sophisticated approach using photoemission spectroscopy (UPS and IPES) would limit the wide access of the investigation. Here, we demonstrate a facile approach to study the electrical and optical quantum efficiencies of a series of conjugated photovoltaic polymer, fullerene and non-fullerene materials. Quantitative values of the exciton binding energy in those prototypical materials were obtained with concise photovoltaic device structure. And the extracted binding energies have excellent agreement with those determined by the conventional photoemission technique. More importantly, our findings can provide valuable information on the excitonic dissociation in the first excited state. Particularly, we find that the high binding energy of some non-fullerene acceptors limits the combination of polymer acceptors for efficiency exciton dissociation. The results bring insight into the engineering of excitonic effect for the development of efficient organic photovoltaic cells.

Keywords: organic photovoltaics, quantum efficiency, exciton binding energy, device physics

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Authors: Dileep Kumar, Janhavi Ramchandra Rao Kumar, Rao

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COVID-19 has ravaged the globe, and it is spreading its Spectre day by day. In the absence of established drugs, this disease has created havoc. Some of the infected persons are symptomatic or asymptomatic. The respiratory system, cardiac system, digestive system, etc. in human beings are affected by this virus. In our present investigation, we have undertaken a study of the Indian Ayurvedic herb, Ocimum sanctum against SARS-CoV-2 using molecular docking and dynamics studies. The docking analysis was performed on the Glide module of Schrödinger suite on two different proteins from SARS-CoV-2 viz. NSP15 Endoribonuclease and spike receptor-binding domain. MM-GBSA based binding free energy calculations also suggest the most favorable binding affinities of carvacrol, β elemene, and β caryophyllene with binding energies of −61.61, 58.23, and −54.19 Kcal/mol respectively with spike receptor-binding domain and NSP15 Endoribonuclease. It rekindles our hope for the design and development of new drug candidates for the treatment of COVID19.

Keywords: molecular docking, COVID-19, ocimum sanctum, binding energy

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Authors: Tivani Phosa Mashamba-Thompson, Mahmoud E. S. Soliman

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To date, the cause of neurodegeneration is not well understood and diseases that stem from neurodegeneration currently have no known cures. Cathepsin B (CB) enzyme is known to be involved in the production of peptide neurotransmitters and toxic peptides in neurodegenerative diseases (NDs). CA-074Me is a membrane-permeable irreversible selective cathepsin B (CB) inhibitor as confirmed by in vivo studies. Due to the lack of the crystal structure, the binding mode of CA-074Me with the human CB at molecular level has not been previously reported. The main aim of this study is to gain an insight into the binding mode of CB CA-074Me to human CB using various computational tools. Herein, molecular dynamics simulations, binding free energy calculations and per-residue energy decomposition analysis were employed to accomplish the aim of the study. Another objective was to identify novel CB inhibitors based on the structure of CA-074Me using fragment based drug design using scaffold hoping drug design approach. Results showed that two of the designed ligands (hit 1 and hit 2) were found to have better binding affinities than the prototype inhibitor, CA-074Me, by ~2-3 kcal/mol. Per-residue energy decomposition showed that amino acid residues Cys29, Gly196, His197 and Val174 contributed the most towards the binding. The Van der Waals binding forces were found to be the major component of the binding interactions. The findings of this study should assist medicinal chemist towards the design of potential irreversible CB inhibitors.

Keywords: cathepsin B, scaffold hopping, docking, molecular dynamics, binding-free energy, neurodegerative diseases

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Authors: Matineh Sadat Hosseini Gheidari, Vahid Reza Yazdanpanah

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In this paper, we used the empirical tight-binding method (ETBM) with sp3s* approximation and considering the first nearest neighbor with spin-orbit interactions in order to model superlattice structure (SLS) of (AlₓGa₁₋ₓAs)ₘ/(GaAs)ₙ grown on GaAs (100) substrate at 300K. In the next step, we investigated the behavior of the energy gap and wavelength of this superlattice in terms of different thicknesses of core materials and Al mole fractions. As a result of this survey, we found out that as the Al composition increases, the energy gap of this superlattice has an upward trend and ranges from 1.42-1.63 eV. Also, according to the wavelength range that we gained from this superlattice in different Al mole fractions and various thicknesses, we can find a suitable semiconductor for a special light-emitting diode (LED) application.

Keywords: energy gap, empirical tight-binding method, light-emitting diode, superlattice, wavelength

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Authors: U. L. Fulco, E. L. Albuquerque, José X. Lima Neto, L. R. Da Silva

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The binding of the nonsteroidal anti-inflammatory drug ibuprofen (IBU) to human serum albumin (HSA) is investigated using density functional theory (DFT) calculations within a fragmentation strategy. Crystallographic data for the IBU–HSA supramolecular complex shows that the ligand is confined to a large cavity at the subdomain IIIA and at the interface between the subdomains IIA and IIB, whose binding sites are FA3/FA4 and FA6, respectively. The interaction energy between the IBU molecule and each amino acid residue of these HSA binding pockets was calculated using the Molecular Fractionation with Conjugate Caps (MFCC) approach employing a dispersion corrected exchange–correlation functional. Our investigation shows that the total interaction energy of IBU bound to HSA at binding sites of the fatty acids FA3/FA4 (FA6) converges only for a pocket radius of at least 8.5 °A, mainly due to the action of residues Arg410, Lys414 and Ser489 (Lys351, Ser480 and Leu481) and residues in nonhydrophobic domains, namely Ile388, Phe395, Phe403, Leu407, Leu430, Val433, and Leu453 (Phe206, Ala210, Ala213, and Leu327), which is unusual. Our simulations are valuable for a better understanding of the binding mechanism of IBU to albumin and can lead to the rational design and the development of novel IBU-derived drugs with improved potency.

Keywords: ibuprofen, human serum albumin, density functional theory, binding energies

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Authors: Bahareh Arghand

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The establishment of rules and regulations for more effective energy-environment interactions are essential to achieving sustainable development. Sustainable development requires mechanisms that can promote compliance in energy-environment conventions. There are many binding agreements and non-binding instruments at regional and international levels on energy and the environment. These conventions try to decrease conflicts of interest between energy, environment and economic by legal principles and practical mechanisms. The major core of conventions is their implementations because the poor implementation and enforcement power affect their success. In this regard, the main goal of this study is proposing the effective implementation mechanisms. Energy service companies' (ESCOs) activities can improve energy efficiency and decrease the environmental degradations. Therefore, it can be proposed and assessed the merit mechanism of ESCO performance as a facilitator to implement energy-environment conventions. An assessment of ESCO performance, including its potentials, problems, and limitations, as a facilitator for effective implementation of the energy-environment convention, is included. This study is oriented towards effective development and application of laws and the function of ESCOs as appropriate economic instruments and facilitator for implementation of energy-environment conventions. The resulting system of close cooperation between the energy-environment conventions and ESCOs is geared toward advancing environmental protection and economic factors by the transfer of environmentally-sound technologies that meet sustainable development objectives.

Keywords: energy-environment conventions, energy service company, facilitator mechanism, sustainable development

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Authors: Arunima Verma, Padmabati Mondal

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Serotonin-receptor binding plays a key role in several neurological and biological processes, including mood, sleep, hunger, cognition, learning, and memory. In this article, we performed molecular dynamics simulation to examine the key residues that play an essential role in the binding of serotonin to the G-protein-coupled 5-HT₁ᴮ receptor (5-HT₁ᴮ R) via electrostatic interactions. An end-point free energy calculation method (MM-PBSA) determines the stability of the 5-HT1B R due to serotonin binding. The single-point mutation of the polar or charged amino acid residues (Asp129, Thr134) on the binding sites and the calculation of binding free energy validate the importance of these residues in the stability of the serotonin-receptor complex. Principal component analysis indicates the serotonin-bound 5-HT1BR is more stabilized than the apo-receptor in terms of dynamical changes. The difference dynamic cross-correlations map shows the correlation between the transmembrane and mini-Go, which indicates signal transduction happening between mini-Go and the receptor. Allosteric communication reveals the key nodes for signal transduction in 5-HT1BR. These results provide useful insights into the signal transduction pathways and mutagenesis study to regulate the functionality of the complex. The developed protocols can be applied to study local non-covalent interactions and long-range allosteric communications in any protein-ligand system for computer-aided drug design.

Keywords: allostery, CADD, MD simulations, MM-PBSA

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Authors: G. Carrero, C. Contreras, M. J. Hendzel

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Linker histones or histones H1 are highly mobile nuclear proteins that regulate the organization of chromatin and limit DNA accessibility by binding to the chromatin structure (DNA and associated proteins). It is known that this binding process is driven by both slow (strong binding) and rapid (weak binding) interactions. However, the exact binding mechanism has not been fully described. Moreover, the existing models only account for one type of bound population that does not distinguish explicitly between the weakly and strongly bound proteins. Thus, we propose different systems of reaction-diffusion equations to describe explicitly the rapid and slow interactions during a FRAP (Fluorescence Recovery After Photobleaching) experiment. We perform a model comparison analysis to characterize the binding mechanism of histone H1 and provide new meaningful biophysical information on the kinetics of histone H1.

Keywords: FRAP (Fluorescence Recovery After Photobleaching), histone H1, histone H1 binding kinetics, linker histone, reaction-diffusion equation

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Authors: Ali M. Elgerbi, Obied A. Alwan, Al-Taher O. Alzwei, Abdurrahim A. Elouzi

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The binding of AFM1 to bacteria in phosphate buffer solution depended on many factors such as: availability of energy, incubation period, species and strain of bacteria. Increase in concentration of sugar showed higher removal of AFM1 and faster than in phosphate buffer alone. With 1.0% glucose lactic acid bacteria and bifidobacteria showed toxin removal ranging from 7.7 to 39.7% whereas with 10.0% glucose the percentage removal was 21.8 to 45.4% at 96 hours of incubation.

Keywords: aflatoxin M1, lactic acid bacteria, bifidobacteria , binding, phosphate buffer

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Authors: Hoa Thi Hoang, Stephan Sass, Michael U. Kumke

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Concanavalin A (conA) is a protein has been widely used in sensor system based on its specific binding to α-D-Glucose or α-D-Manose. For glucose sensor using conA, either fluoresence based techniques with intensity based or lifetime based are used. In this research, liposomes made from phospholipids were used as a biomimetic membrane system. In a first step, novel building blocks containing perylene labeled glucose units were added to the system and used to decorate the surface of the liposomes. Upon the binding between rhodamine labeled con A to the glucose units at the biomimetic membrane surface, a Förster resonance energy transfer system can be formed which combines unique fluorescence properties of perylene (e.g., high fluorescence quantum yield, no triplet formation) and its high hydrophobicity for efficient anchoring in membranes to form a novel probe for the investigation of sugar-driven binding reactions at biomimetic surfaces. Two glucose-labeled perylene derivatives were synthesized with different spacer length between the perylene and glucose unit in order to probe the binding of conA. The binding interaction was fully characterized by using high-end fluorescence techniques. Steady-state and time-resolved fluorescence techniques (e.g., fluorescence depolarization) in combination with single-molecule fluorescence spectroscopy techniques (fluorescence correlation spectroscopy, FCS) were used to monitor the interaction with conA. Base on the fluorescence depolarization, the rotational correlation times and the alteration in the diffusion coefficient (determined by FCS) the binding of the conA to the liposomes carrying the probe was studied. Moreover, single pair FRET experiments using pulsed interleaved excitation are used to characterize in detail the binding of conA to the liposome on a single molecule level avoiding averaging out effects.

Keywords: concanavalin A, FRET, sensor, biomimetic membrane

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Authors: Rohit Singh Dangi, Ravi Kant Pal, Monica Sundd

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Acyl-CoA binding protein (ACBP) is a housekeeping protein which functions as an intracellular carrier of acyl-CoA esters. Given the fact that the amastigote stage (blood stage) of Leishmania depends largely on fatty acids as the energy source, of which a large part is derived from its host, these proteins might have an important role in its survival. In Leishmania major, genome sequencing suggests the presence of six ACBPs, whose function remains largely unknown. For functional and structural characterization, one of the ACBP genes was cloned, and the protein was expressed and purified heterologously. Acyl-CoA ester binding and stoichiometry were analyzed by isothermal titration calorimetry and Dynamic light scattering. Our results shed light on high affinity of ACBP towards longer acyl-CoA esters, such as myristoyl-CoA to arachidonoyl-CoA with single binding site. To understand the binding mechanism & dynamics, Nuclear magnetic resonance assignments of this protein are being done. The protein's crystal structure was determined at 1.5Å resolution and revealed a classical topology for ACBP, containing four alpha-helical bundles. In the binding pocket, the loop between the first and the second helix (16 – 26AA) is four residues longer from other extensively studied ACBPs (PfACBP) and it curls upwards towards the pantothenate moiety of CoA to provide a large tunnel space for long acyl chain insertion.

Keywords: acyl-coa binding protein (ACBP), acyl-coa esters, crystal structure, isothermal titration, calorimetry, Leishmania

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Authors: Sarka Keprdova, Jiri Bydzovsky

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This article describes to what extent the addition of energy by-products into the structures of the technical hemp filling materials influence their properties. The article focuses on the changes in physical-mechanical and thermal technical properties of materials after the addition of ash or FBC ash or slag in the binding component of material. Technical hemp filling materials are made of technical hemp shives bonded by the mixture of cement and dry hydrate lime. They are applicable as fillers of vertical or horizontal structures or roofs. The research used eight types of energy by-products of power or heating plants in the Czech Republic. Secondary energy products were dispensed in three different percentage ratios as a replacement of cement in the binding component. Density, compressive strength and determination of the coefficient of thermal conductivity after 28, 60 and 90 days of curing in a laboratory environment were determined and subsequently evaluated on the specimens produced.

Keywords: ash, binder, cement, energy by-product, FBC ash (fluidized bed combustion ash), filling materials, shives, slag, technical hemp

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Authors: Mohammed Auwal Ibrahim, Aminu Mohammed

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Stigmasterol has previously been reported to possess antitrypanosomal activity using in vitro and in vivo models. However, the mechanism of antitrypanosomal activity is yet to be elucidated. In the present study, molecular docking was used to decipher the mode of interaction and binding affinity of stigmasterol to three known antitrypanosomal drug targets viz; adenosine kinase, ornithine decarboxylase and triose phosphate isomerase. Stigmasterol was found to bind to the selected trypanosomal enzymes with minimum binding energy of -4.2, -6.5 and -6.6 kcal/mol for adenosine kinase, ornithine decarboxylase, and triose phosphate isomerase respectively. However, hydrogen bond was not involved in the interaction of stigmasterol with all the three enzymes, but hydrophobic interaction seemed to play a vital role in the binding phenomenon which was predicted to be non-competitive like type of inhibition. It was concluded that binding to the three selected enzymes, especially triose phosphate isomerase, might be involved in the antitrypanosomal activity of stigmasterol but not mediated via a hydrogen bond interaction.

Keywords: antitrypanosomal, in silico, molecular docking, stigmasterol

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Authors: Fatih Ozaydin

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Quantum Fisher information (QFI) is a multipartite entanglement witness and recently it has been studied extensively with separability and entanglement in the focus. On the other hand, bound entanglement is a special phenomena observed in mixed entangled states. In this work, we study the QFI of W states under a four-dimensional entanglement binding channel. Starting with initally pure W states of several qubits, we find how the QFI decreases as two qubits of the W state is subject to entanglement binding. We also show that as the size of the W state increases, the effect of entanglement binding is decreased.

Keywords: Quantum Fisher information, W states, bound entanglement, entanglement binding

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Authors: Wei-Ting Kuo, Feng-Huei Lin

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Epidermal growth factor receptor (EGFR) is often constitutively stimulated in cancer owing to the binding of ligands such as epidermal growth factor (EGF), so it is necessary to investigate the interaction between EGFR and its targeting biomolecules which were over ligands binding. This study would focus on the binding affinity and adhesion force of two targeting products anti-EGFR monoclonal antibody (mAb) and peptide A to EGFR comparing with EGF. Surface plasmon resonance (SPR) was used to obtain the equilibrium dissociation constant to evaluate the binding affinity. Atomic force microscopy (AFM) was performed to detect adhesion force. The result showed that binding affinity of mAb to EGFR was higher than that of EGF to EGFR, and peptide A to EGFR was lowest. The adhesion force between EGFR and mAb that was higher than EGF and peptide A to EGFR was lowest. From the studies, we could conclude that mAb had better adhesion force and binding affinity to EGFR than that of EGF and peptide A. SPR and AFM could confirm the interaction between receptor and targeting ligand easily and carefully. It provide a platform to screen ligands for receptor targeting and drug delivery.

Keywords: adhesion force, binding affinity, epidermal growth factor receptor, target molecule

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Authors: Taimur Khan, Zakirullah, Muhammad Shahab

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The SARS-CoV-2 variant BA.2.86 (Omicron) has emerged with unique mutations that may increase its transmission and infectivity. This study investigates how these mutations alter the Omicron receptor-binding domain's interaction network and dynamic properties (RBD) compared to the wild-type virus, focusing on its binding affinity to the human ACE2 (hACE2) receptor. Protein-protein docking and all-atom molecular dynamics simulations were used to analyze structural and dynamic differences. Despite the structural similarity to the wild-type virus, the Omicron variant exhibits a distinct interaction network involving new residues that enhance its binding capacity. The dynamic analysis reveals increased flexibility in the RBD, particularly in loop regions crucial for hACE2 interaction. Mutations significantly alter the secondary structure, leading to greater flexibility and conformational adaptability compared to the wild type. Binding free energy calculations confirm that the Omicron RBD has a higher binding affinity (-70.47 kcal/mol) to hACE2 than the wild-type RBD (-61.38 kcal/mol). These results suggest that the altered interaction network and enhanced dynamics of the Omicron variant contribute to its increased infectivity, providing insights for the development of targeted therapeutics and vaccines.

Keywords: SARS-CoV-2, molecular dynamic simulation, receptor binding domain, vaccine

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Authors: Agnieszka Krzemińska, Katarzyna Świderek, Vicente Molinier, Piotr Paneth

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In order to understand in details the interactions between ligands and the enzyme isotope effects were studied between clinically used drugs that bind in the active site of Human Immunodeficiency Virus Reverse Transcriptase, HIV-1 RT, as well as triazole-based inhibitor that binds in the allosteric pocket of this enzyme. The magnitudes and origins of the resulting binding isotope effects were analyzed. Subsequently, binding isotope effect of the same triazole-based inhibitor bound in the active site were analyzed and compared. Together, these results show differences in binding origins in two sites of the enzyme and allow to analyze binding mode and place of newly synthesized inhibitors. Typical protocol is described below on the example of triazole ligand in the allosteric pocket. Triazole was docked into allosteric cavity of HIV-1 RT with Glide using extra-precision mode as implemented in Schroedinger software. The structure of HIV-1 RT was obtained from Protein Data Bank as structure of PDB ID 2RKI. The pKa for titratable amino acids was calculated using PROPKA software, and in order to neutralize the system 15 Cl- were added using tLEaP package implemented in AMBERTools ver.1.5. Also N-terminals and C-terminals were build using tLEaP. The system was placed in 144x160x144Å3 orthorhombic box of water molecules using NAMD program. Missing parameters for triazole were obtained at the AM1 level using Antechamber software implemented in AMBERTools. The energy minimizations were carried out by means of a conjugate gradient algorithm using NAMD. Then system was heated from 0 to 300 K with temperature increment 0.001 K. Subsequently 2 ns Langevin−Verlet (NVT) MM MD simulation with AMBER force field implemented in NAMD was carried out. Periodic Boundary Conditions and cut-offs for the nonbonding interactions, range radius from 14.5 to 16 Å, are used. After 2 ns relaxation 200 ps of QM/MM MD at 300 K were simulated. The triazole was treated quantum mechanically at the AM1 level, protein was described using AMBER and water molecules were described using TIP3P, as implemented in fDynamo library. Molecules 20 Å apart from the triazole were kept frozen, with cut-offs established on range radius from 14.5 to 16 Å. In order to describe interactions between triazole and RT free energy of binding using Free Energy Perturbation method was done. The change in frequencies from ligand in solution to ligand bounded in enzyme was used to calculate binding isotope effects.

Keywords: binding isotope effects, molecular dynamics, HIV, reverse transcriptase

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Authors: Mahasen M. Abdel Mageed, H. S. Zaghloul

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Annihilations, phase shifts, scattering lengths, and elastic cross sections of low energy positrons scattering from magnesium atoms were studied using the least-squares variational method (LSVM). The possibility of positron binding to the magnesium atoms is investigated. A trial wavefunction is suggested to represent e+-Mg elastic scattering and scattering parameters were derived to estimate the binding energy and annihilation rates. The trial function is taken to depend on several adjustable parameters and is improved iteratively by increasing the number of terms. The present results have the same behavior as reported semi-empirical, theoretical, and experimental results. Especially, the estimated positive scattering length supports the possibility of positron-magnesium bound state system that was confirmed in previous experimental and theoretical work.

Keywords: bound wavefunction, positron annihilation, scattering phase shift, scattering length

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Authors: Stephen Eyije Abechi, Casimir Emmanuel Gimba, Zaharaddeen Nasiru Garba, Sani Shamsudeen, David Ebuka Authur

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Corrosion inhibition of mild steel in acid medium using Acalypha chamaedrifolia leaves extract as potential green inhibitor was investigated. Gravimetric (weight loss) technique was used for the corrosion studies. Mild steel coupons of 2cm × 1cm × 0.27 cm dimensions were exposed for varying durations of between 24 to 120 hours, in 1M HCl medium containing a varying concentrations of the leaves extract (0.25g/L, - 1.25g/L). The results show that corrosion rates dropped from a value of 0.49 mgcm-2hr-1 for the uninhibited medium to a value of 0.15 mgcm-2hr-1 for the inhibited medium of 1M HCl in 0.25 g/l of the extract. Values of corrosion inhibition efficiencies of 70.38-85.11% were observed as the concentration of the inhibitor were increased from 0.25g/L, - 1.25g/L. Corrosion Inhibition was found to increase with increase in immersion time and temperature. The magnitude of the Ea indicates that the interaction between the metal surface and the inhibitor was chemisorptions. The Adsorption process fit into the Langmuir isotherm model with a correlation coefficient of 0.97. Evidence from molecular dynamics model shows that Methyl stearate (Line 5) and (3Z, 13Z)-2-methyloctadeca-3,13-dien-1-ol (line 11) were found to have the highest binding energy of -197.69 ± 3.12 and-194.56 ± 10.04 in kcal/mol respectively. The binding energy of these compounds indicates that they would be a very good corrosion inhibitor for mild steel and other Fe related materials.

Keywords: binding energy, corrosion, inhibitor, langmuir isotherm, mild steel

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Authors: Stephen Eyije Abechi, Casimir Emmanuel Gimba, Zaharaddeen Nasiru Garba, Sani Shamsudeen, David Ebuka Authur

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The mechanisms of corrosion inhibition of mild steel in acid medium using Acalypha chamaedrifolia leaves extract as potential green inhibitor were investigated. Gravimetric (weight loss) technique was used for the corrosion studies. Mild steel coupons of 2cm × 1cm × 0.27 cm dimensions were exposed for varying durations of between 24 to 120 hours, in 1M HCl medium containing a varying concentrations of the leaves extract (0.25g/L, - 1.25g/L). The results show that corrosion rates dropped from a value of 0.49 mgcm-2hr-1 for the uninhibited medium to a value of 0.15 mgcm-2hr-1 for the inhibited medium of 1M HCl in 0.25 g/l of the extract. Values of corrosion inhibition efficiencies of 70.38-85.11% were observed as the concentration of the inhibitor were increased from 0.25g/L, - 1.25g/L. Corrosion Inhibition was found to increase with increase in immersion time and temperature. The magnitude of the Ea indicates that the interaction between the metal surface and the inhibitor was chemisorptions. The Adsorption process fit into the Langmuir isotherm model with a correlation coefficient of 0.97. Evidence from molecular dynamics model shows that Methyl stearate (Line 5) and (3Z, 13Z)-2-methyloctadeca-3,13-dien-1-ol (line 11) were found to have the highest binding energy of -197.69 ± 3.12 and-194.56 ± 10.04 in kcal/mol respectively. The binding energy of these compounds indicates that they would be a very good corrosion inhibitor for mild steel and other Fe related materials.

Keywords: binding energy, corrosion, inhibitor, Langmuir isotherm, mild steel.

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Authors: Naiduwadura Ivon Upekala De Silva, Nathan Lehman, Talia Fargason, Trenton Paul, Zihan Zhang, Jun Zhang

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SRSF1 governs splicing of over 1,500 mRNA transcripts. SRSF1 contains two RNA-recognition motifs (RRMs) and a C-terminal Arg/Ser-rich region (RS). It has been thought that SRSF1 RRMs exclusively recognize single-stranded exonic splicing enhancers, while RS lacks RNA-binding specificity. With our success in solving the insolubility problem of SRSF1, we can explore the unknown RNA-binding landscape of SRSF1. We find that SRSF1 RS prefers purine over pyrimidine. Moreover, SRSF1 binds to the G-quadruplex (GQ) from the ARPC2 mRNA, with both RRMs and RS being crucial. Our binding assays show that the traditional RNA-binding sites on the RRM tandem and the Arg in RS are responsible for GQ binding. Interestingly, our FRET and circular dichroism data reveal that SRSF1 unfolds the ARPC2 GQ, with RS leading unfolding and RRMs aiding. Our saturation transfer difference NMR results discover that Arg residues in SRSF1 RS interact with the guanine base but with other nucleobases, underscoring the uniqueness of the Arg/guanine interaction. Our luciferase assays confirm that SRSF1 can alleviate the inhibitory effect of GQ on gene expression in the cell. Given the prevalence of RNA GQ and SR proteins, our findings unveil unexplored SR protein functions with broad implications in RNA splicing and translation.

Keywords: SR, SRSF!, RNA G-quadruplex, unfolding, RNA binding

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Authors: Amit Chaudhary, B. S. Yadav, P. K. Maurya, A. M., S. Srivastava, S. Singh, A. Mani

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Cold shock protein A (CspA) is major cold inducible protein present in Escherichia coli. The protein is involved in stabilizing secondary structure of RNA by working as chaperone during cold temperature. Two RNA binding motifs play key role in the stabilizing activity. This study aimed to investigate implications of low temperature on structure and RNA binding activity of E. coli CspA. Molecular dynamics simulations were performed to compare the stability of the protein at 37°C and 10 °C. The protein was mutated at RNA binding motifs and docked with RNA to assess the stability of both complexes. Results suggest that CspA as well as CspA-RNA complex is more stable at low temperature. It was also confirmed that RNP1 and RNP2 play key role in RNA binding.

Keywords: CspA, homology modelling, mutation, molecular dynamics simulation

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Authors: A. Jamsheera, F. Arjmand, D. K. Mohapatra

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Small molecules binding to specific sites along DNA molecule are considered as potential chemotherapeutic agents. Their role as mediators of key biological functions and their unique intrinsic properties make them particularly attractive therapeutic agents. Keeping in view, novel dipeptide complexes Cu(II)-Val-Pro (1), Zn(II)-Val-Pro (2), Cu(II)-Ala-Pro (3) and Zn(II)-Ala-Pro (4) were synthesized and thoroughly characterized using different spectroscopic techniques including elemental analyses, IR, NMR, ESI–MS and molar conductance measurements. The solution stability study carried out by UV–vis absorption titration over a broad range of pH proved the stability of the complexes in solution. In vitro DNA binding studies of complexes 1–4 carried out employing absorption, fluorescence, circular dichroism and viscometric studies revealed the binding of complexes to DNA via groove binding. UV–vis titrations of 1–4 with mononucleotides of interest viz., 5´-GMP and 5´-TMP were also carried out. The DNA cleavage activity of the complexes 1 and 2 were ascertained by gel electrophoresis assay which revealed that the complexes are good DNA cleavage agents and the cleavage mechanism involved a hydrolytic pathway. Furthermore, in vitro antitumor activity of complex 1 was screened against human cancer cell lines of different histological origin.

Keywords: dipeptide Cu(II) and Zn(II) complexes, DNA binding profile, pBR322 DNA cleavage, in vitro anticancer activity

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Authors: Amir Zeb, Shailima Rampogu, Minky Son, Ayoung Baek, Sang H. Yoon, Keun W. Lee

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Neurotoxic insults activate calpain, which in turn produces truncated p25 from p35. p25 forms hyperactivated Cdk5/p25 complex, and thereby induces severe neuropathological aberrations including hyperphosphorylated tau, neuroinflammation, apoptosis, and neuronal death. Inhibition of Cdk5/p25 complex alleviates aberrant phosphorylation of tau to mitigate AD pathology. PHA-793887 and Roscovitine have been investigated as selective inhibitors of Cdk5/p25 with IC50 values 5nM and 160nM, respectively, but their mechanistic studies remain unknown. Herein, computational simulations have explored the binding mode and interaction mechanism of PHA-793887 and Roscovitine with Cdk5/p25. Docking results suggested that PHA-793887 and Rsocovitine have occupied the ATP-binding site of Cdk5 and obtained highest docking (GOLD) score of 66.54 and 84.03, respectively. Furthermore, molecular dynamics (MD) simulation demonstrated that PHA-793887 and Roscovitine established stable RMSD of 1.09 Å and 1.48 Å with Cdk5/p25, respectively. Profiling of polar interactions suggested that each inhibitor formed hydrogen bonds (H-bond) with catalytic residues of Cdk5 and could remain stable throughout the molecular dynamics simulation. Additionally, binding free energy calculation by molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) suggested that PHA-793887 and Roscovitine had lowest binding free energies of -150.05 kJ/mol and -113.14 kJ/mol, respectively with Cdk5/p25. Free energy decomposition demonstrated that polar energy by H-bond between the Glu81 of Cdk5 and PHA-793887 is the essential factor to make PHA-793887 highly selective towards Cdk5/p25. Overall, this study provided substantial evidences to explore mechanistic interactions of the selective inhibitors of Cdk5/p25 and could be used as fundamental considerations in the development of structure-based selective inhibitors of Cdk5/p25.

Keywords: Cdk5/p25 inhibition, molecular modeling of Cdk5/p25, PHA-793887 and roscovitine, selective inhibition of Cdk5/p25

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Authors: Hyun Joon Chang, Jae In Kim, Sungsoo Na

Abstract:

Kinesin-1 (hereafter called kinesin) is a molecular motor protein that moves cargos toward the end of microtubules using the energy of adenosine triphosphate (ATP) hydrolysis. When kinesin is inactive, its tail autoinhibits the motor chain in order to prevent from reacting with the ATP by cross-linking of the tail domain to the motor domains at two positions. However, the morphological study of kinesin during autoinhibition is yet remained obscured. In this study, we report the effect of the binding site of the tail domain using the normal mode analysis of the elastic network model on kinesin in the tail-free form and tail-bind form. Considering the relationship between the connectivity of conventional network model with respect to the cutoff length and the functionality of the binding site of the tail, we revaluated the network model to observe the key role of the tail domain in its structural aspect. Contingent on the existence of the tail domain, the results suggest the morphological stability of the motor domain. Furthermore, employing the results from normal mode analysis, we have determined the strain energy of the neck linker, an essential portion of the motor domain for ATP hydrolysis. The results of the neck linker also converge to the same indication, i.e. the morphological analysis of the motor domain.

Keywords: elastic network model, Kinesin-1, autoinhibition

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Authors: Abayomi T. Ogunjimi, Gbenga Alebiowu

Abstract:

Mechanical properties of paracetamol tablets containing Neem (Azadirachta indica) gum were compared with standard Acacia gum BP as binder. Two dimensionless binding quantities BEN and BEC were used in assessing the influence of binder type on two mechanical properties, Tensile Strength (TS) and Brittle Fracture Index (BFI). The two quantities were also used to assess the influence of relative density and binder concentration on TS and BFI as well as compare Binding Efficiencies (BE). The result shows that TS is dependent on relative density, binder type and binder concentration while BFI is dependent on the binder type and binder concentration; and that although, the inclusion of NMG in a paracetamol tablet formulation may not enhance the TS of the tablets produced, however it will decrease the tendency of the tablets to cap or laminate. This work concludes that BEN may be useful in quantitative assessment while BEC may be appropriate for qualitative assessment.

Keywords: binding efficiency, brittle fracture index, dimensionless binding, tensile strength

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Authors: Sirilak Kongkaew, Pathumwadee Yodmanee, Nopporn Kaiyawet, Arthitaya Meeprasert, Thanyada Rungrotmongkol, Toshikatsu Kaburaki, Hiroshi Noguchi, Fujio Takeuch, Nawee Kungwan, Supot Hannongbua

Abstract:

Behçet’s disease (BD) is a genetic autoimmune expressed by multisystemic inflammatory disorder mostly occurred at the skin, joints, gastrointestinal tract, and genitalia, including ocular, oral, genital, and central nervous systems. Most BD patients in Japan and Korea were strongly indicated by the genetic factor namely HLA-B*51 (especially, HLA-B*51:01) marker in HMC class I, while HLA-A*26:01 allele has been detected from the BD patients in Greek, Japan, and Taiwan. To understand the selective binding of the MICA-TM peptide towards the HLAs associated with BD, the molecular dynamics simulations were applied on the four HLA alleles (B*51:01, B*35:01, A*26:01, and A*11:01) in complex with such peptide. As a result, the key residues in the binding groove of HLA protein which play an important role in the MICA-TM peptide binding and stabilization were revealed. The Van der Waals force was found to be the main protein-protein interaction. Based on the binding free energy prediction by MM/PBSA method, the MICA-TM peptide interacted stronger to the HLA alleles associated to BD in the identical class by 7-12 kcal/mol. The obtained results from the present study could help to differentiate the HLA alleles and explain a source of Behçet’s disease.

Keywords: Behçet’s disease, MD simulations, HMC class I, autoimmune

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Authors: Andra Blumberga, Uldis Bariss, Anna Kubule, Dagnija Blumberga

Abstract:

European Union Energy Efficiency Directive provides a set of binding energy efficiency measures to reach. Each of the member states can use either energy efficiency obligation scheme or alternative policy measures or combination of both. Latvian government has decided to divide savings among obligation scheme (65%) and alternative measures (35%). This decision might lead to significant energy tariff increase hence impact on the national economy. To assess impact of alternative policy measures focusing on energy management scheme based on ISO 50001 and ability to decrease share of obligation scheme a System Dynamics modeling was used. Simulation results show that energy efficiency goal can be met with alternative policy measure to large energy consumers in industrial, tertiary and public sectors by applying the energy tax exemption for implementers of energy management system. A delay in applying alternative policy measures plays very important role in reaching the energy efficiency goal. One year delay in implementation of this policy measure reduces cumulative energy savings from 2016 to 2017 from 5200 GWh to 3000 GWh in 2020.

Keywords: system dynamics, energy efficiency, policy measure, energy management system, obligation scheme

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Authors: Yaxuan Wang

Abstract:

It has long been a mystery that why the Mongolian possessive suffix, which is constrained by Condition A of binding theory, has the ability to probe a potential antecedent outside of its binding domain. This squib argues that binding theory alone is not sufficient to explain the linguistic facts and proposes an analysis adopting the Agree operation. The current analysis correctly predicts all the possible and impossible structures, with an additional hypothesis that Mongolian possessive suffixes serve as an antecedent for PROs in adjunct. The findings thus provide insights into how Agree operates in Mongolian language.

Keywords: syntax, Mongolian, agreement, possessive particles

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Authors: Nusrat Masood, Vijaya Dubey, Suaib Luqman

Abstract:

Caspase 3, a member of cysteine-aspartic acid protease family, is an imperative indicator for cell death particularly when substantiating apoptosis. Thus, caspase 3 is an interesting target for the discovery and development of anticancer agent. We adopted a four level assessment of both terpenoids and flavonoids and thus experimentally performed the enzymatic assay in cell free system as well as in cancer cell line which was validated through real time expression and molecular interaction studies. A significant difference was observed with both the class of natural products indicating terpenoids as better activators of caspase 3 compared to flavonoids both in the cell free system as well as in cell lines. The expression analysis, activation constant and binding energy also correlate well with the enzyme activity. Overall, terpenoids had an unswerving effect on caspase 3 in all the tested system while flavonoids indirectly affect enzyme activity.

Keywords: Caspase 3, terpenoids, flavonoids, activation constant, binding energy

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