Binding free energy calculations using MMPB/GBSA approaches for PAMAM-G4-drug complexes at neutral, basic and acid pH conditions

Bello, Martiniano; Romero-Castro, Aurelio; Rodríguez-Fonseca, Rolando Alberto; Rodrigues, João; Sánchez-Espinosa, Victor Armando; Correa‐Basurto, José

doi:10.1016/j.jmgm.2017.07.017

Cited by 17 publications

(12 citation statements)

References 73 publications

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“…34 The binding free energy of each protein-ligand complex was determined as described elsewhere. 35 2.1.6. Docking and MD simulations of peptides on MHC-II and MHC-I.…”

Section: Methodsmentioning

confidence: 99%

In silico and in vivo studies of gp120-HIV-derived peptides in complex with G4-PAMAM dendrimers

et al. 2020

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“…34 The binding free energy of each protein-ligand complex was determined as described elsewhere. 35 2.1.6. Docking and MD simulations of peptides on MHC-II and MHC-I.…”

Section: Methodsmentioning

confidence: 99%

In silico and in vivo studies of gp120-HIV-derived peptides in complex with G4-PAMAM dendrimers

et al. 2020

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“…The Visual Molecular Dynamics (VMD) 67 package was used for the visual inspection of the simulated systems. To calculate the binding enthalpy the well-known "Molecular Mechanics / Generalized Born model augmented with the solvent accessible surface area term (GBSA)" approach has been considered, as employed in earlier literature to estimate and compare binding energies calculated from MD simulations 43,[68][69][70][71][72][73] .…”

Section: Molecular Dynamicsmentioning

confidence: 99%

Elucidating the role of surface chemistry on cationic phosphorus dendrimer–siRNA complexation

et al. 2018

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In the field of dendrimers targeting small interfering RNA (siRNA) delivery, dendrimer structural properties, such as the flexibility/rigidity ratio, play a crucial role in the efficiency of complexation. However, advances in organic chemistry have enabled the development of dendrimers that differ only by a single atom on their surface terminals. This is the case for cationic phosphorus dendrimers functionalized with either pyrrolidinium (DP) or morpholinium (DM) terminal groups. This small change was shown to strongly affect the dendrimer-siRNA complexation, leading to more efficient anti-inflammatory effects in the case of DP. Reasons for this different behavior can hardly be inferred only by biological in vitro and in vivo experiments due to the high number of variables and complexity of the investigated biological system. However, an understanding of how small chemical surface changes may completely modify the overall dendrimer-siRNA complexation is a significant breakthrough towards the design of efficient dendrimers for nucleic acid delivery. Herein, we present experimental and computational approaches based on isothermal titration calorimetry and molecular dynamics simulations to elucidate the molecular reasons behind different efficiencies and activities of DP and DM. Results of the present research highlight how chemical surface modifications may drive the overall dendrimer-siRNA affinity by influencing enthalpic and entropic contributions of binding free energy. Moreover, this study elucidates molecular reasons related to complexation stoichiometry that may be crucial in determining the dendrimer complexation efficiency.

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“…The binding free energy calculation of each complex was performed based on Molecular Mechanics-Poisson Boltzmann Surface Area (MM-PBSA) using MMPBSA.py method, and the decomposition energy of the key residues was calculated using per-residue decomposition energy module of AMBER14. The binding and decomposition energies were extracted from the trajectories of the last 20 ns of the simulations ( Amir-Hassan et al., 2017 ; Martínez-Muñoz et al., 2017 ).…”

Section: Methodsmentioning

confidence: 99%

Docking based screening and molecular dynamics simulations to identify potential selective PDE4B inhibitor

Al-Nema

Gaurav

Lee

2020

Heliyon

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Inhibition of phosphodiesterase 4 (PDE4) is a promising therapeutic approach for the treatment of inflammatory pulmonary disorders, i.e. asthma and chronic obstructive pulmonary disease. However, the treatment with non-selective PDE4 inhibitors is associated with side effects such as nausea and vomiting. Among the subtypes of PDE4 inhibited by these inhibitors, PDE4B is expressed in immune, inflammatory and airway smooth muscle cells, whereas, PDE4D is expressed in the area postrema and nucleus of the solitary tract. Thus, PDE4D inhibition is responsible for the emetic response. In this regard, a selective PDE4B inhibitor is expected to be a potential drug candidate for the treatment of inflammatory pulmonary disorders. Therefore, a shared feature pharmacophore model was developed and used as a query for the virtual screening of Maybridge and SPECS databases. A number of filters were applied to ensure only compounds with drug-like properties were selected. Accordingly, nine compounds have been identified as final hits, where HTS04529 showed the highest affinity and selectivity for PDE4B over PDE4D in molecular docking. The docked complexes of HTS04529 with PDE4B and PDE4D were subjected to molecular dynamics simulations for 100ns to assess their binding stability. The results showed that HTS04529 was bound tightly to PDE4B and formed a more stable complex with it than with PDE4D.

show abstract

Binding free energy calculations using MMPB/GBSA approaches for PAMAM-G4-drug complexes at neutral, basic and acid pH conditions

Cited by 17 publications

References 73 publications

In silico and in vivo studies of gp120-HIV-derived peptides in complex with G4-PAMAM dendrimers

In silico and in vivo studies of gp120-HIV-derived peptides in complex with G4-PAMAM dendrimers

Elucidating the role of surface chemistry on cationic phosphorus dendrimer–siRNA complexation

Docking based screening and molecular dynamics simulations to identify potential selective PDE4B inhibitor

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