scholarly journals Microsecond simulation unravel the structural dynamics of SARS-CoV-2 Spike-C-terminal cytoplasmic tail (residues 1242-1273)

2021 ◽  
Author(s):  
Prateek Kumar ◽  
Taniya Bhardwaj ◽  
Neha Garg ◽  
Rajanish Giri
Keyword(s):  
Structural Dynamics ◽  
Viral Proteins ◽  
Spike Protein ◽  
Temperature Dependent ◽  
Replica Exchange Molecular Dynamics ◽  
Structural Conformation ◽  
Human Coronaviruses ◽  
Function Relationship ◽  
Dynamics Simulations ◽  
Relationship Of

AbstractSpike protein of human coronaviruses has been a vital drug and vaccine target. The multifunctionality of this protein including host receptor binding and apoptosis has been proved in several coronaviruses. It also interacts with other viral proteins such as membrane (M) protein through its C-terminal domain. The specific dibasic motif signal present in cytosolic region at C-terminal of spike protein helps it to localize within the endoplasmic reticulum (ER). However, the structural conformation of cytosolic region is not known in SARS-CoV-2 using which it interacts with other proteins and transporting vesicles. Therefore, we have demonstrated the conformation of cytosolic region and its dynamics through computer simulations up to microsecond timescale using OPLS and CHARMM forcefields. The simulations have revealed the unstructured conformation of cytosolic region (residues 1242-1273). Also, in temperature dependent replica-exchange molecular dynamics simulations it has shown to form secondary structures. We believe that our findings will surely help us understand the structure-function relationship of the spike protein’s cytosolic region.

scholarly journals CriTER-A: A Novel Temperature-Dependent Noncoding RNA Switch in the Telomeric Transcriptome of Chironomus riparius

2021 ◽  
Vol 22 (19) ◽  
pp. 10310
Author(s):  
Cristina Romero-López ◽  
Alfredo Berzal-Herranz ◽  
José Luis Martínez-Guitarte ◽  
Mercedes de la Fuente
Keyword(s):  
Thermal Stress ◽  
Noncoding Rna ◽  
Relative Proportion ◽  
Chironomus Riparius ◽  
Temperature Dependent ◽  
Differential Behaviour ◽  
High Sequence Homology ◽  
Function Relationship ◽  
Relationship Of

The telomeric transcriptome of Chironomus riparius has been involved in thermal stress response. One of the telomeric transcripts, the so-called CriTER-A variant, is highly overexpressed upon heat shock. On the other hand, its homologous variant CriTER-B, which is the most frequently encoded noncoding RNA in the telomeres of C. riparius, is only slightly affected by thermal stress. Interestingly, both transcripts show high sequence homology, but less is known about their folding and how this could influence their differential behaviour. Our study suggests that CriTER-A folds as two different conformers, whose relative proportion is influenced by temperature conditions. Meanwhile, the CriTER-B variant shows only one dominant conformer. Thus, a temperature-dependent conformational equilibrium can be established for CriTER-A, suggesting a putative functional role of the telomeric transcriptome in relation to thermal stress that could rely on the structure–function relationship of the CriTER-A transcripts.

scholarly journals Advances in Molecular Dynamics Simulations and Enhanced Sampling Methods for the Study of Protein Systems

2020 ◽  
Vol 21 (17) ◽  
pp. 6339
Author(s):  
Raudah Lazim ◽  
Donghyuk Suh ◽  
Sun Choi
Keyword(s):  
Molecular Dynamics ◽  
Md Simulation ◽  
Enhanced Sampling ◽  
Structure Based Drug Design ◽  
Simulation Tools ◽  
Computer Calculations ◽  
Function Relationship ◽  
Dynamics Simulations ◽  
Relationship Of

Molecular dynamics (MD) simulation is a rigorous theoretical tool that when used efficiently could provide reliable answers to questions pertaining to the structure-function relationship of proteins. Data collated from protein dynamics can be translated into useful statistics that can be exploited to sieve thermodynamics and kinetics crucial for the elucidation of mechanisms responsible for the modulation of biological processes such as protein-ligand binding and protein-protein association. Continuous modernization of simulation tools enables accurate prediction and characterization of the aforementioned mechanisms and these qualities are highly beneficial for the expedition of drug development when effectively applied to structure-based drug design (SBDD). In this review, current all-atom MD simulation methods, with focus on enhanced sampling techniques, utilized to examine protein structure, dynamics, and functions are discussed. This review will pivot around computer calculations of protein-ligand and protein-protein systems with applications to SBDD. In addition, we will also be highlighting limitations faced by current simulation tools as well as the improvements that have been made to ameliorate their efficiency.

scholarly journals Computational Study on Temperature Driven Structure–Function Relationship of Polysaccharide Producing Bacterial Glycosyl Transferase Enzyme

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1771
Author(s):  
Patricio González-Faune ◽  
Ignacio Sánchez-Arévalo ◽  
Shrabana Sarkar ◽  
Krishnendu Majhi ◽  
Rajib Bandopadhyay ◽  
...  
Keyword(s):  
Structural Integrity ◽  
Computational Study ◽  
In Silico Analysis ◽  
Temperature Dependent ◽  
Bacterial Exopolysaccharide ◽  
Function Relationship ◽  
Industrial Level ◽  
Relationship Of ◽  
Bacterial Sources ◽  
Silico Analysis

Glycosyltransferase (GTs) is a wide class of enzymes that transfer sugar moiety, playing a key role in the synthesis of bacterial exopolysaccharide (EPS) biopolymer. In recent years, increased demand for bacterial EPSs has been observed in pharmaceutical, food, and other industries. The application of the EPSs largely depends upon their thermal stability, as any industrial application is mainly reliant on slow thermal degradation. Keeping this in context, EPS producing GT enzymes from three different bacterial sources based on growth temperature (mesophile, thermophile, and hyperthermophile) are considered for in silico analysis of the structural–functional relationship. From the present study, it was observed that the structural integrity of GT increases significantly from mesophile to thermophile to hyperthermophile. In contrast, the structural plasticity runs in an opposite direction towards mesophile. This interesting temperature-dependent structural property has directed the GT–UDP-glucose interactions in a way that thermophile has finally demonstrated better binding affinity (−5.57 to −10.70) with an increased number of hydrogen bonds (355) and stabilizing amino acids (Phe, Ala, Glu, Tyr, and Ser). The results from this study may direct utilization of thermophile-origin GT as best for industrial-level bacterial polysaccharide production.

Investigating targets for neuropharmacological intervention by molecular dynamics simulations

2019 ◽  
Vol 47 (3) ◽  
pp. 909-918
Author(s):  
Giulia Rossetti ◽  
Achim Kless ◽  
Luhua Lai ◽  
Tiago F. Outeiro ◽  
Paolo Carloni
Keyword(s):  
Molecular Dynamics ◽  
Disease Onset ◽  
Physiological Saline ◽  
Diagnostic Tools ◽  
Biologically Relevant ◽  
Neuroactive Drugs ◽  
Function Relationship ◽  
Dynamics Simulations ◽  
Relationship Of ◽  
Insight Into

Abstract Medical research has identified over 500 brain disorders. Among these, there are still only very few neuropathologies whose causes are fully understood and, consequently, very few drugs whose mechanism of action is known. No FDA drug has been identified for major neurodegenerative diseases, such as Alzheimer's and Parkinson's. We still lack effective treatments and strategies for modulating progression or even early neurodegenerative disease onset diagnostic tools. A great support toward the highly needed identification of neuroactive drugs comes from computer simulation methods and, in particular, from molecular dynamics (MD). This provides insight into structure–function relationship of a target and predicts structure, dynamics and energetics of ligand/target complexes under biologically relevant conditions like temperature and physiological saline concentration. Here, we present examples of the predictive power of MD for neuroactive ligands/target complexes. This brief survey from our own research shows the usefulness of partnerships between academia and industry, and from joint efforts between experimental and theoretical groups.

Identification of Potential Inhibitors for Targets Involved in Dengue Fever

2020 ◽  
Vol 20 (19) ◽  
pp. 1742-1760
Author(s):  
Anusuya Shanmugam ◽  
Chandrasekaran Ramakrishnan ◽  
Devadasan Velmurugan ◽  
M. Michael Gromiha
Keyword(s):  
Drug Discovery ◽  
Medicinal Plants ◽  
Dengue Infection ◽  
Viral Proteins ◽  
Methyl Transferase ◽  
Small Molecule Drug ◽  
Function Relationship ◽  
Global Threat ◽  
Potential Inhibitors ◽  
Relationship Of

Lethality due to dengue infection is a global threat. Nearly 400 million people are affected every year, which approximately costs 500 million dollars for surveillance and vector control itself. Many investigations on the structure-function relationship of proteins expressed by the dengue virus are being made for more than a decade and had come up with many reports on small molecule drug discovery. In this review, we present a detailed note on viral proteins and their functions as well as the inhibitors discovered/designed so far using experimental and computational methods. Further, the phytoconstituents from medicinal plants, specifically the extract of the papaya leaves, neem and bael, which combat dengue infection via dengue protease, helicase, methyl transferase and polymerase are summarized.

scholarly journals Infectivity of dengue virus serotypes 1 and 2 is correlated to E protein intrinsic dynamics but not to envelope conformations

2018 ◽  
Author(s):  
Kamal Kant SHARMA ◽  
Xin-Xiang LIM ◽  
Sarala Neomi TANTIRIMUDALIGE ◽  
Anjali Gupta ◽  
Jan K MARZINEK ◽  
...  
Keyword(s):  
Structural Dynamics ◽  
Conformational Changes ◽  
Large Scale ◽  
Morphological Changes ◽  
Divalent Cations ◽  
Virulent Strain ◽  
Viral Envelope ◽  
Temperature Dependent ◽  
Dengue Virus Serotypes ◽  
Dynamics Simulations

Dengue is a mosquito-borne virus with dire health and economic impact. Dengue is responsible for an estimated ~390 million infections per year, with Dengue 2 (DENV2) being the most virulent strain among the four serotypes. Interestingly, it is also for strains of this serotype that temperature-dependent large scale morphological changes, termed as 'breathing', have been observed. Although, the structure of these morphologies has been solved to 3.5 Angstrom resolution, the dynamics of the viral envelope are unknown. Here, we combine fluorescence and mass spectrometry and molecular dynamics simulations to provide insights into DENV2 structural dynamics in comparison to DENV1. We observe hitherto unseen conformational changes and structural dynamics of the DENV2 envelope that are influenced by both temperature and divalent cations. Our results show that for DENV2 and DENV1 the intrinsic dynamics but not the specific morphologies are correlated to viral infectivity.

Structural dynamics of P-type ATPase ion pumps

2019 ◽  
Vol 47 (5) ◽  
pp. 1247-1257 ◽  
Author(s):  
Mateusz Dyla ◽  
Sara Basse Hansen ◽  
Poul Nissen ◽  
Magnus Kjaergaard
Keyword(s):  
Structural Dynamics ◽  
Single Molecule ◽  
New Technologies ◽  
Atp Hydrolysis ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Time Resolved ◽  
Dynamics Simulations ◽  
Types Of Information ◽  
P Type

Abstract P-type ATPases transport ions across biological membranes against concentration gradients and are essential for all cells. They use the energy from ATP hydrolysis to propel large intramolecular movements, which drive vectorial transport of ions. Tight coordination of the motions of the pump is required to couple the two spatially distant processes of ion binding and ATP hydrolysis. Here, we review our current understanding of the structural dynamics of P-type ATPases, focusing primarily on Ca2+ pumps. We integrate different types of information that report on structural dynamics, primarily time-resolved fluorescence experiments including single-molecule Förster resonance energy transfer and molecular dynamics simulations, and interpret them in the framework provided by the numerous crystal structures of sarco/endoplasmic reticulum Ca2+-ATPase. We discuss the challenges in characterizing the dynamics of membrane pumps, and the likely impact of new technologies on the field.

Real-Space X-Ray Pair Distribution Function Analysis and Molecular-Dynamics Modelling of Diflunisal Channel Hydrates

2020 ◽  
Author(s):  
Anuradha Pallipurath ◽  
Francesco Civati ◽  
Jonathan Skelton ◽  
Dean Keeble ◽  
Clare Crowley ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Distribution Function ◽  
Structural Dynamics ◽  
First Principles ◽  
Pair Distribution Function ◽  
Function Analysis ◽  
Real Space ◽  
X Ray ◽  
Dynamics Modelling ◽  
Dynamics Simulations

X-ray pair distribution function analysis is used with first-principles molecular dynamics simulations to study the co-operative H<sub>2</sub>O binding, structural dynamics and host-guest interactions in the channel hydrate of diflunisal.

Sign in / Sign up

Export Citation Format

Share Document