Construction of the small intestine on molecular dynamics simulation and preliminary exploration of drug intestinal absorption prediction

Shi, Yanshuang; Sheng, Mengke; Zhou, Qing; Liao, Yuyao; Lv, Lijing; Yang, Jiaqi; Peng, Xinhui; Cen, Shuai; Dai, Xing‐Xing; Shi, Xiaowen

doi:10.1016/j.compbiolchem.2022.107724

Cited by 2 publications

(3 citation statements)

References 27 publications

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“…First, CHARMM-GUI was used to construct lateral membranes of the small intestinal epithelial cell (Feng et al, 2023), respectively. According to our previous research (Shi et al, 2022), the cell membrane models with different lipid ratios were built. Six hundred lipid molecules were placed in a 14 × 14 × 8 nm box, with 22.5 Å water layer thickness and 0.15 mol/L Na + , Cl − .…”

Section: The Construction Of Membranesmentioning

confidence: 99%

A hybrid evaluation of the intestinal absorption performance of compounds from molecular structure

Sheng,

Ma,

et al. 2024

Chem Biol Drug Des

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Intestinal absorption of compounds is significant in drug research and development. To evaluate this efficiently, a method combining mathematical modeling and molecular simulation was proposed, from the perspective of molecular structure. Based on the quantitative structure–property relationship study, the model between molecular structure and their apparent permeability coefficients was successfully constructed and verified, predicting intestinal absorption of drugs and interpreting decisive structural factors, such as AlogP98, Hydrogen bond donor and Ellipsoidal volume. The molecules with strong lipophilicity, less hydrogen bond donors and receptors, and small molecular volume are more easily absorbed. Then, the molecular dynamics simulation and molecular docking were utilized to study the mechanism of differences in intestinal absorption of drugs and investigate the role of molecular structure. Results indicated that molecules with strong lipophilicity and small volume interacted with the membrane at a lower energy and were easier to penetrate the membrane. Likewise, they had weaker interaction with P‐glycoprotein and were easier to escape from it and harder to export from the body. More in, less out, is the main reason these molecules absorb well.

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Section: The Construction Of Membranesmentioning

confidence: 99%

A hybrid evaluation of the intestinal absorption performance of compounds from molecular structure

Sheng,

Ma,

et al. 2024

Chem Biol Drug Des

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“…13 The phospholipids have been used to construct cell membranes of small intestinal cells, which are close to the real cell state. 14 The membrane model made of phosphatidylcholines, typically 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), is commonly employed in passive membrane permeability studies. This model simplifies the complexities of real membranes, making it convenient to investigate the interaction of the membrane and peptides.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the liposome bilayer thickness could be varied in a controlled manner due to regions of packed chains . The phospholipids have been used to construct cell membranes of small intestinal cells, which are close to the real cell state . The membrane model made of phosphatidylcholines, typically 1,2-dipalmitoyl- sn -glycero-3-phosphatidylcholine (DPPC), is commonly employed in passive membrane permeability studies.…”

Section: Introductionmentioning

confidence: 99%

Understanding the Transepithelial Transport and Transbilayer Diffusion of the Antihypertensive Peptide Asn-Cys-Trp: Insights from Caco-2 Cell Monolayers and the DPPC Model Membrane

Wu,

Jiang,

Zhang

et al. 2024

J. Agric. Food Chem.

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Understanding the transport mechanism of the peptide Asn-Cys-Trp (NCW) is crucial to improving its intestinal absorption and bioavailability. This study investigated the absorption of NCW through Caco-2 cell monolayers and its interaction with the DPPC bilayers. Results revealed that after a 3 h incubation, the Papp (AP-BL) and Papp (BL-AP) values of NCW at a concentration of 5 mmol/L were (22.24 ± 4.52) × 10 −7 and (6.63 ± 2.31) × 10 −7 cm/s, respectively, with the transport rates of 1.59 ± 0.32 and 0.62 ± 0.20%, indicating its moderate absorption. NCW was found to be transported via PepT1 and paracellular transport pathways, as evidenced by the significant impact of Gly-Pro and cytochalasin D on the Papp values. Moreover, NCW upregulated ZO-1 mRNA expression. Further investigation of the ZO-1-mediated interaction between NCW and tight junction proteins will contribute to a better understanding of the paracellular transport mechanism of NCW. The interaction between NCW and the DPPC bilayers was predominantly driven by entropy. NCW permeated the bilayers through electrostatic, hydrogen bonding, and hydrophobic interactions, resulting in increased fluidity, flexibility, and disorder as well as phase transition and phase separation of the bilayers.

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Construction of the small intestine on molecular dynamics simulation and preliminary exploration of drug intestinal absorption prediction

Cited by 2 publications

References 27 publications

A hybrid evaluation of the intestinal absorption performance of compounds from molecular structure

A hybrid evaluation of the intestinal absorption performance of compounds from molecular structure

Understanding the Transepithelial Transport and Transbilayer Diffusion of the Antihypertensive Peptide Asn-Cys-Trp: Insights from Caco-2 Cell Monolayers and the DPPC Model Membrane

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