Delineating the impact of pathogenic mutations on the conformational dynamics of HDL’s vital protein ApoA1: a combined computational and molecular dynamic simulation approach

Bhale, Aishwarya; Venkataraman, Krishnan

doi:10.1080/07391102.2023.2191131

Cited by 2 publications

(2 citation statements)

References 79 publications

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“…This study was undertaken to identify small molecules that have the ability to modulate the structure and function of a pathogenic apoA-I variant, apoA-I[L178P]. Lipid-free apoA-I displays a high degree of conformational plasticity ( 41 ) and natural occurring point mutations, such as the L178P, have been shown to induce local but also global effects on the structure of protein ( 23 , 42 ). Lipid-free apoA-I has a direct physiologically relevant role since it promotes ABCA1-mediated efflux of phospholipids and cholesterol, a step that is critical both for de novo HDL biogenesis by hepatocytes and for atheroprotection by intimal macrophages ( 10 , 11 ).…”

Section: Discussionmentioning

confidence: 99%

Library screening identifies commercial drugs as potential structure correctors of abnormal apolipoprotein A-I

Gkolfinopoulou,

Bourtsala,

Georgiadou

et al. 2024

Journal of Lipid Research

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Section: Discussionmentioning

confidence: 99%

Library screening identifies commercial drugs as potential structure correctors of abnormal apolipoprotein A-I

Gkolfinopoulou,

Bourtsala,

Georgiadou

et al. 2024

Journal of Lipid Research

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“…APOA1 is a necessary component of HDL particles. It plays a key role in the biosynthesis of HDL, cholesterol transport, and RCT [ 52 ]. It also has anti-inflammatory, anti-atherogenic, anti-apoptotic, and anti-thrombotic properties.…”

Section: Discussionmentioning

confidence: 99%

Identifying the natural products in the treatment of atherosclerosis by increasing HDL-C level based on bioinformatics analysis, molecular docking, and in vitro experiment

Chen,

Zhang,

Sun

et al. 2023

J Transl Med

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Background Previous studies have demonstrated that high-density lipoprotein cholesterol (HDL-C) plays an anti-atherosclerosis role through reverse cholesterol transport. Several studies have validated the efficacy and safety of natural products in treating atherosclerosis (AS). However, the study of raising HDL-C levels through natural products to treat AS still needs to be explored. Methods The gene sets associated with AS were collected and identified by differential gene analysis and database query. By constructing a protein–protein interaction (PPI) network, the core submodules in the network are screened out. At the same time, by calculating node importance (Nim) in the PPI network of AS disease and combining it with Kyoto Encyclopedia of genes and genomes (KEGG) pathways enrichment analysis, the key target proteins of AS were obtained. Molecular docking is used to screen out small natural drug molecules with potential therapeutic effects. By constructing an in vitro foam cell model, the effects of small molecules on lipid metabolism and key target expression of foam cells were investigated. Results By differential gene analysis, 451 differential genes were obtained, and a total of 313 disease genes were obtained from 6 kind of databases, then 758 AS-related genes were obtained. The enrichment analysis of the KEGG pathway showed that the enhancement of HDL-C level against AS was related to Lipid and atherosclerosis, Cholesterol metabolism, Fluid shear stress and atherosclerosis, PPAR signaling pathway, and other pathways. Then we intersected 31 genes in the core module of the PPI network, the top 30 genes in Nims, and 32 genes in the cholesterol metabolism pathway, and finally found 3 genes. After the above analysis and literature collection, we focused on the following three related gene targets: APOA1, LIPC, and CETP. Molecular docking showed that Genistein has a good binding affinity for APOA1, CETP, and LIPC. In vitro, experiments showed that Genistein can up-regulated APOA1, LIPC, and CETP levels. Conclusions Based on our research, Genistein may have the effects of regulating HDL-C and anti-atherosclerosis. Its mechanism of action may be related to the regulation of LIPC, CETP, and APOA1 to improve lipid metabolism.

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Delineating the impact of pathogenic mutations on the conformational dynamics of HDL’s vital protein ApoA1: a combined computational and molecular dynamic simulation approach

Cited by 2 publications

References 79 publications

Library screening identifies commercial drugs as potential structure correctors of abnormal apolipoprotein A-I

Library screening identifies commercial drugs as potential structure correctors of abnormal apolipoprotein A-I

Identifying the natural products in the treatment of atherosclerosis by increasing HDL-C level based on bioinformatics analysis, molecular docking, and in vitro experiment

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