Molecular Dynamics Simulations: Advances and Applications

Filipe, Hugo A. L.; Loura, Luís M. S.

doi:10.3390/molecules27072105

Cited by 89 publications

(21 citation statements)

References 8 publications

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“…In addition, to understand the macromolecular system at atomic level, the application of MD simulation is also helpful to decipher the hidden or undetected states of system under consideration [ 73 , 74 , 75 ]. Thus, as end-point free energy methods [ 76 , 77 , 78 ], MD simulations in combination with binding free energy methods have been comprehensively used in structure-based drug design to determine the thermodynamic properties of the macromolecular system, including stability, affinity, and free energy decomposition analysis [ 75 ].…”

Section: Resultsmentioning

confidence: 99%

Computational Investigations on the Natural Small Molecule as an Inhibitor of Programmed Death Ligand 1 for Cancer Immunotherapy

Kumar

Moustafa

Sahoo

et al. 2022

Life

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Several therapeutic monoclonal antibodies approved by the FDA are available against the PD-1/PD-L1 (programmed death 1/programmed death ligand 1) immune checkpoint axis, which has been an unprecedented success in cancer treatment. However, existing therapeutics against PD-L1, including small molecule inhibitors, have certain drawbacks such as high cost and drug resistance that challenge the currently available anti-PD-L1 therapy. Therefore, this study presents the screening of 32,552 compounds from the Natural Product Atlas database against PD-L1, including three steps of structure-based virtual screening followed by binding free energy to refine the ideal conformation of potent PD-L1 inhibitors. Subsequently, five natural compounds, i.e., Neoenactin B1, Actinofuranone I, Cosmosporin, Ganocapenoid A, and 3-[3-hydroxy-4-(3-methylbut-2-enyl)phenyl]-5-(4-hydroxybenzyl)-4-methyldihydrofuran-2(3H)-one, were collected based on the ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling and binding free energy (>−60 kcal/mol) for further computational investigation in comparison to co-crystallized ligand, i.e., JQT inhibitor. Based on interaction mapping, explicit 100 ns molecular dynamics simulation, and end-point binding free energy calculations, the selected natural compounds were marked for substantial stability with PD-L1 via intermolecular interactions (hydrogen and hydrophobic) with essential residues in comparison to the JQT inhibitor. Collectively, the calculated results advocate the selected natural compounds as the putative potent inhibitors of PD-L1 and, therefore, can be considered for further development of PD-L1 immune checkpoint inhibitors in cancer immunotherapy.

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Section: Resultsmentioning

confidence: 99%

Computational Investigations on the Natural Small Molecule as an Inhibitor of Programmed Death Ligand 1 for Cancer Immunotherapy

Kumar

Moustafa

Sahoo

et al. 2022

Life

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“…For a representative view of the current status of MD, the reader is referred, for instance, to the special issue in Ref. [ 59 ]. In the context of our work, the MD simulations clearly establish that the main difference between both fragments arises when comparing the maximum forces that each one may generate.…”

Section: Discussionmentioning

confidence: 99%

Differences in the Elastomeric Behavior of Polyglycine-Rich Regions of Spidroin 1 and 2 Proteins

et al. 2022

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Two different polyglycine-rich fragments were selected as representatives of major ampullate gland spidroins (MaSp) 1 and 2 types, and their behavior in a water-saturated environment was simulated within the framework of molecular dynamics (MD). The selected fragments are found in the sequences of the proteins MaSp1a and MaSp2.2a of Argiope aurantia with respective lengths of 36 amino acids (MaSp1a) and 50 amino acids (MaSp2.2s). The simulation took the fully extended β-pleated conformation as reference, and MD was used to determine the equilibrium configuration in the absence of external forces. Subsequently, MD were employed to calculate the variation in the distance between the ends of the fragments when subjected to an increasing force. Both fragments show an elastomeric behavior that can be modeled as a freely jointed chain with links of comparable length, and a larger number of links in the spidroin 2 fragment. It is found, however, that the maximum recovery force recorded from the spidroin 2 peptide (Fmax ≈ 400 pN) is found to be significantly larger than that of the spidroin 1 (Fmax ≈ 250 pN). The increase in the recovery force of the spidroin 2 polyglycine-rich fragment may be correlated with the larger values observed in the strain at breaking of major ampullate silk fibers spun by Araneoidea species, which contain spidroin 2 proteins, compared to the material produced by spider species that lack these spidroins (RTA-clade).

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“…Molecular dynamics simulation is a technique based on classical Newton mechanics to simulate molecular motion on atomic scale in a computer . The interaction between atoms is simulated by giving each biomolecule an appropriate force field.…”

Section: Molecular Dynamics Simulationmentioning

confidence: 99%

Application of Molecular Simulation Methods in Food Science: Status and Prospects

et al. 2023

J. Agric. Food Chem.

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Molecular simulation methods, such as molecular docking, molecular dynamic (MD) simulation, and quantum chemical (QC) calculation, have become popular as characterization and/or virtual screening tools because they can visually display interaction details that in vitro experiments can not capture and quickly screen bioactive compounds from large databases with millions of molecules. Currently, interdisciplinary research has expanded molecular simulation technology from computer aided drug design (CADD) to food science. More food scientists are supporting their hypotheses/results with this technology. To understand better the use of molecular simulation methods, it is necessary to systematically summarize the latest applications and usage trends of molecular simulation methods in the research field of food science. However, this type of review article is rare. To bridge this gap, we have comprehensively summarized the principle, combination usage, and application of molecular simulation methods in food science. We also analyzed the limitations and future trends and offered valuable strategies with the latest technologies to help food scientists use molecular simulation methods.

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Molecular Dynamics Simulations: Advances and Applications

Abstract: Molecular dynamics (MD) simulations have led to great advances in many scientific disciplines, such as chemical physics, materials science, and biophysics. [...]

Cited by 89 publications

References 8 publications

Computational Investigations on the Natural Small Molecule as an Inhibitor of Programmed Death Ligand 1 for Cancer Immunotherapy

Computational Investigations on the Natural Small Molecule as an Inhibitor of Programmed Death Ligand 1 for Cancer Immunotherapy

Differences in the Elastomeric Behavior of Polyglycine-Rich Regions of Spidroin 1 and 2 Proteins

Application of Molecular Simulation Methods in Food Science: Status and Prospects

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