Simulating Time-Resolved Dynamics of Biomolecular Systems

Aranda-García, David; Torrens‐Fontanals, Mariona; Medel-Lacruz, Brian; Lopez-Balastegui, Marta; Peralta-García, Alejandro; Dieguez-Eceolaza, Miguel; Morales-Pastor, Adrián; Sotillo-Núñez, David; Abbondandolo, Davide; Stępniewski, Tomasz Maciej; Selent, Jana

doi:10.1016/b978-0-12-820472-6.00214-0

Cited by 3 publications

(3 citation statements)

References 114 publications

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“…MD simulation is a potent approach for investigating the biomolecular structure, interactions, the dynamics of biological systems in‐silico 35,36 . To complete the results derived from molecular docking, we performed an MD simulation.…”

Section: Resultsmentioning

confidence: 99%

“…MD simulation is a potent approach for investigating the biomolecular structure, interactions, the dynamics of biological systems in-silico. 35,36 To complete the results derived from molecular docking, we performed an MD simulation. Compared to molecular docking, the main advantage of MD simulation is that it not only investigates proteins' interactions at the atomic level but also provides a physiological condition that is close to the cellular mode.…”

Section: Simulation Analysismentioning

confidence: 99%

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The role of S477N mutation in the molecular behavior of SARS‐CoV‐2 spike protein: An in‐silico perspective

Mondeali

Etemadi

Barkhordari

et al. 2023

J of Cellular Biochemistry

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The attachment of SARA-CoV-2 happens between ACE2 and the receptor binding domain (RBD) on the spike protein. Mutations in this domain can affect the binding affinity of the spike protein for ACE2. S477N, one of the most common mutations reported in the recent variants, is located in the RBD.Today's computational approaches in biology, especially during the SARS-CoV-2 pandemic, assist researchers in predicting a protein's behavior in contact with other proteins in more detail. In this study, we investigated the interactions of the S477N-hACE2 in silico to find the impact of this mutation on its binding affinity for ACE2 and immunity responses using dynamics simulation, protein-protein docking, and immunoinformatics methods. Our computational analysis revealed an increased binding affinity of N477 for ACE2. Four new hydrogen and hydrophobic bonds in the mutant RBD-ACE2 were formed (with S19 and Q24 of ACE2), which do not exist in the wild type. Also, the protein spike structure in this mutation was associated with an increase in stabilization and a decrease in its fluctuations at the atomic level. N477 mutation can be considered as the cause of increased escape from the immune system through MHC-II.

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Section: Resultsmentioning

confidence: 99%

Section: Simulation Analysismentioning

confidence: 99%

The role of S477N mutation in the molecular behavior of SARS‐CoV‐2 spike protein: An in‐silico perspective

Mondeali

Etemadi

Barkhordari

et al. 2023

J of Cellular Biochemistry

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“…A main challenge of studying allostery in GPCRs is to monitor ACNs and their alterations related to specific signaling conditions at appropriate spatiotemporal resolution. Molecular dynamics (MD) simulations have emerged as an invaluable tool for complementing static structural, biophysical and biochemical data [12][13][14] to access the proper resolution levels. They allow for the exploration of protein dynamics at an atomic level, offering insights into the conformational changes at microsecond timescale and corresponding intramolecular networks under conditions of signaling bias 15,16 .…”

Section: Introductionmentioning

confidence: 99%

Multiple triggers converge to preferential effector coupling in the CB2R through a complex allosteric communication network

Morales-Pastor,

Miljus,

Stepniewski

et al. 2024

Preprint

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G protein-coupled receptors are important therapeutic drug targets for a wide range of diseases. Their ability to preferentially engage specific signaling pathways over others can be exploited to design drugs that target only disease-associated pathways leading to an improved safety profile. However, the underlying molecular mechanisms for preferential pathway engagement are complex and remain largely elusive. To elucidate the multifaceted actions at the receptor level that lead to preferential coupling, we employ a combination of techniques. Our approach integrates systematic mutagenesis of the CB2R and comprehensive profiling of Gαi2 and β-arrestin1 engagements with computer simulations to track mutant-induced impacts on receptor dynamics. Most importantly, our research discloses multiple triggers on a complex allosteric communication network (ACN) that converge to preferential CB2R coupling by modulating evolutionary conserved motifs (e.g., CWxP, NPxxY, sodium binding site). Potent triggers for a preferential Gαi2 response exhibit high levels of connectivity and are located in proximity to connections with high information transmission. Our insights highlight the complexity of GPCR signaling and can guide the rational design of drug candidates tailored to evoke specific functional responses that can enhance the precision and efficacy of therapeutic interventions.

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In vivo and in silico investigations on the efficacy of albendazole against Enterocytozoon hepatopenaei (EHP) infecting Penaeus vannamei

et al. 2023

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Simulating Time-Resolved Dynamics of Biomolecular Systems

Cited by 3 publications

References 114 publications

The role of S477N mutation in the molecular behavior of SARS‐CoV‐2 spike protein: An in‐silico perspective

The role of S477N mutation in the molecular behavior of SARS‐CoV‐2 spike protein: An in‐silico perspective

Multiple triggers converge to preferential effector coupling in the CB2R through a complex allosteric communication network

In vivo and in silico investigations on the efficacy of albendazole against Enterocytozoon hepatopenaei (EHP) infecting Penaeus vannamei

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