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Insights into the Molecular Mechanisms of Protein-Ligand Interactions by Molecular Docking and Molecular Dynamics Simulation: A Case of Oligopeptide Binding Protein.

ABSTRACT: Protein-ligand interactions are a necessary prerequisite for signal transduction, immunoreaction, and gene regulation. Protein-ligand interaction studies are important for understanding the mechanisms of biological regulation, and they provide a theoretical basis for the design and discovery of new drug targets. In this study, we analyzed the molecular interactions of protein-ligand which was docked by AutoDock 4.2 software. In AutoDock 4.2 software, we used a new search algorithm, hybrid algorithm of random drift particle swarm optimization and local search (LRDPSO), and the classical Lamarckian genetic algorithm (LGA) as energy optimization algorithms. The best conformations of each docking algorithm were subjected to molecular dynamic (MD) simulations to further analyze the molecular mechanisms of protein-ligand interactions. Here, we analyze the binding energy between protein receptors and ligands, the interactions of salt bridges and hydrogen bonds in the docking region, and the structural changes during complex unfolding. Our comparison of these complexes highlights differences in the protein-ligand interactions between the two docking methods. It also shows that salt bridge and hydrogen bond interactions play a crucial role in protein-ligand stability. The present work focuses on extracting the deterministic characteristics of docking interactions from their dynamic properties, which is important for understanding biological functions and determining which amino acid residues are crucial to docking interactions.

SUBMITTER: Fu Y

PROVIDER: S-EPMC6305025 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Insights into the Molecular Mechanisms of Protein-Ligand Interactions by Molecular Docking and Molecular Dynamics Simulation: A Case of Oligopeptide Binding Protein.

Fu Yi Y Zhao Ji J Chen Zhiguo Z

Computational and mathematical methods in medicine 20181204

Protein-ligand interactions are a necessary prerequisite for signal transduction, immunoreaction, and gene regulation. Protein-ligand interaction studies are important for understanding the mechanisms of biological regulation, and they provide a theoretical basis for the design and discovery of new drug targets. In this study, we analyzed the molecular interactions of protein-ligand which was docked by AutoDock 4.2 software. In AutoDock 4.2 software, we used a new search algorithm, hybrid algori ...[more]

PMID: 30627209

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Project description:The urea transporter UT-B1, encoded by the SLC14A1 gene, has been hypothesized to be a significant protein whose deficiency and dysfunction contribute to the pathogenesis of bladder cancer and many other diseases. Several studies reported the association of genetic alterations in the SLC14A1 (UT-B1) gene with bladder carcinogenesis, suggesting a need for thorough characterization of the UT-B1 protein's coding and non-coding variants. This study used various computational techniques to investigate the commonly occurring germ-line missense and non-coding SNPs (ncSNPs) of the SLC14A1 gene (UT-B1) for their structural, functional, and molecular implications for disease susceptibility and dysfunctionality. SLC14A1 missense variants, primarily identified from the ENSEMBL genome browser, were screened through twelve functionality prediction tools leading to two variants D280Y (predicted detrimental by maximum tools) and D280N (high global MAF) for rs1058396. Subsequently, the ConSurf and NetSurf tools revealed the D280 residue to be in a variable site and exposed on the protein surface. According to I-Mutant2.0 and MUpro, both variants are predicted to cause a significant effect on protein stability. Analysis of molecular docking anticipated these two variants to decrease the binding affinity of UT-B1 protein for the examined ligands to a significant extent. Molecular dynamics also disclosed the possible destabilization of the UT-B1 protein due to single nucleotide polymorphism compared to wild-type protein which may result in impaired protein function. Furthermore, several non-coding SNPs were estimated to affect transcription factor binding and regulation of SLC14A1 gene expression. Additionally, two ncSNPs were found to affect miRNA-based post-transcriptional regulation by creating new seed regions for miRNA binding. This comprehensive in-silico study of SLC14A1 gene variants may serve as a springboard for future large-scale investigations examining SLC14A1 polymorphisms.

Dataset Information

Insights into the Molecular Mechanisms of Protein-Ligand Interactions by Molecular Docking and Molecular Dynamics Simulation: A Case of Oligopeptide Binding Protein.

Publications

Insights into the Molecular Mechanisms of Protein-Ligand Interactions by Molecular Docking and Molecular Dynamics Simulation: A Case of Oligopeptide Binding Protein.

Similar Datasets

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