DNA Structural Distortions Induced by a Monofunctional Trinuclear Platinum Complex with Various Cross-Links Using Molecular Dynamics Simulation

Li, Chaoqun; Zhao, Xiaojia; Liu, Wei; Yin, Fangqian; Hu, Junping; Zhang, Guangjie; Chen, Guangju

doi:10.1021/acs.jcim.0c00002

Cited by 12 publications

(8 citation statements)

References 53 publications

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“…All MTPC-DNA adducts exhibit distinct conformational variations, including bending and twisting motions. The results provide a deeper understanding of MTPC-induced DNA structure deformation with various cross-links at the nucleotide scale, which provides a basis for the development of novel anticancer compounds [ 34 ].…”

Section: Modifications Of Platinum- and Palladium-based Moleculesmentioning

confidence: 99%

Platinum and Palladium Complexes as Promising Sources for Antitumor Treatments

Czarnomysy

Radomska

Szewczyk

et al. 2021

IJMS

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There is a need for new, safer, and more effective agents to treat cancer. Cytostatics that have transition metals at their core have attracted renewed interest from scientists. Researchers are attempting to use chemotherapeutics, such as cisplatin, in combination therapy (i.e., in order to enhance their effectiveness). Moreover, studies are being carried out to modify molecules, by developing them into multinuclear structures, linking different compounds to commonly used drugs, or encapsulating them in nanoparticles to improve pharmacokinetic parameters, and increase the selectivity of these drugs. Therefore, we attempted to organize recent drug findings that contain palladium and platinum atoms in their structures.

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Section: Modifications Of Platinum- and Palladium-based Moleculesmentioning

confidence: 99%

Platinum and Palladium Complexes as Promising Sources for Antitumor Treatments

Czarnomysy

Radomska

Szewczyk

et al. 2021

IJMS

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“…After modeling the missing residues, the Mn 2+ metal center of the coproheme in each model was replaced by an Fe 3+ . For MD and TMD simulations, all model systems were explicitly solvated by using transferable intermolecular potential 3P (TIP3P) water inside a rectangular box large enough to ensure that the solvent shell was extended to 10 Å in all directions of this model [ 30 , 31 ]. The details of the construction processes for these models can be found in each section.…”

Section: Methodsmentioning

confidence: 99%

“…MD simulations, including minimization, heating and equilibration, were performed using the Amber20 package (version 20, URL: ambermd.org, San Francisco, CA, USA) with the classical AMBER force field ff14SB [ 31 ]. The details of the MD procedure are given in the Supplementary Materials [ 15 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. The CPPTRAJ and PTRAJ utilities embedded in the Amber20 program were used to obtain the root mean square deviation (RMSD), average structures, hydrogen bond and salt bridge interactions from the trajectories [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

Reorienting Mechanism of Harderoheme in Coproheme Decarboxylase—A Computational Study

Liu

Pang

Song

et al. 2022

IJMS

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Coproheme decarboxylase (ChdC) is an important enzyme in the coproporphyrin-dependent pathway (CPD) of Gram-positive bacteria that decarboxylates coproheme on two propionates at position 2 and position 4 sequentially to generate heme b by using H2O2 as an oxidant. This work focused on the ChdC from Geobacillus stearothermophilus (GsChdC) to elucidate the mechanism of its sequential two-step decarboxylation of coproheme. The models of GsChdC in a complex with substrate and reaction intermediate were built to investigate the reorienting mechanism of harderoheme. Targeted molecular dynamics simulations on these models validated that harderoheme is able to rotate in the active site of GsChdC with a 19.06-kcal·mol−1 energy barrier after the first step of decarboxylation to bring the propionate at position 4 in proximity of Tyr145 to continue the second decarboxylation step. The harderoheme rotation mechanism is confirmed to be much easier than the release–rebinding mechanism. In the active site of GsChdC, Trp157 and Trp198 comprise a “gate” construction to regulate the clockwise rotation of the harderoheme. Lys149 plays a critical role in the rotation mechanism, which not only keeps the Trp157–Trp198 “gate” from being closed but also guides the propionate at position 4 through the gap between Trp157 and Trp198 through a salt bridge interaction.

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“…MD simulations for these models, including minimization, heating and equilibration, were performed by using the sander module of AMBER16 package with a classical AMBER parm99 [49,50]. The details of the MD procedure are given in the electronic supplementary material.…”

Section: Molecular Dynamics Simulation and Zdockmentioning

confidence: 99%

Insights into the aggregation mechanism of RNA recognition motif domains in TDP-43: a theoretical exploration

Liu

Jiang

et al. 2021

R. Soc. open sci.

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The transactive response DNA-binding protein 43 (TDP-43) is associated with several diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) due to pathogenic aggregations. In this work, we examined the dimer, tetramer and hexamer models built from the RRM domains of TDP-43 using molecular dynamics simulations in combination with the protein–protein docking. Our results showed that the formations of the dimer models are mainly achieved by the interactions of the RRM1 domains. The parallel β-sheet layers between the RRM1 domains provide most of the binding sites in these oligomer models, and thus play an important role in the aggregation process. The approaching of the parallel β-sheet layers from small oligomer models gradually expand to large ones through the allosteric communication between the α1/α2 helices of the RRM1 domains, which maintains the binding affinities and interactions in the larger oligomer models. Using the repeatable-superimposing method based on the tetramer models, we proposed a new aggregation mechanism of RRM domains in TDP-43, which could well characterize the formation of the large aggregation models with the repeated, helical and rope-like structures. These new insights help to understand the amyloid-like aggregation phenomena of TDP-43 protein in ALS and FTLD diseases.

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DNA Structural Distortions Induced by a Monofunctional Trinuclear Platinum Complex with Various Cross-Links Using Molecular Dynamics Simulation

Cited by 12 publications

References 53 publications

Platinum and Palladium Complexes as Promising Sources for Antitumor Treatments

Platinum and Palladium Complexes as Promising Sources for Antitumor Treatments

Reorienting Mechanism of Harderoheme in Coproheme Decarboxylase—A Computational Study

Insights into the aggregation mechanism of RNA recognition motif domains in TDP-43: a theoretical exploration

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