Boosting the Full Potential of PyMOL with Structural Biology Plugins

Rosignoli, Serena; Paiardini, Alessandro

doi:10.3390/biom12121764

Cited by 54 publications

(25 citation statements)

References 104 publications

(114 reference statements)

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“…The structure of co-crystal ligands were downloaded from Pubchem ( https://pubchem.ncbi.nlm.nih.gov/ ) [ 13 ]. Then, the molecular visualization system PyMOL2 ( https://pymol.org/2/ ) was used to remove water and organic ligand from the target proteins and the result was saved in the PDBQT file format [ 25 ]. AutoDock 1.5.7 software was then used to add all the polar hydrogens and target protein was chosen as a receptor [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

Potential mechanisms of osthole against bladder cancer cells based on network pharmacology, molecular docking, and experimental validation

Jiang

Zhang

Wang

et al. 2023

BMC Complement Med Ther

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Background Osthole was traditionally used in treatment for various diseases. However, few studies had demonstrated that osthole could suppress bladder cancer cells and its mechanism was unclear. Therefore, we performed a research to explore the potential mechanism for osthole against bladder cancer. Methods Internet web servers SwissTargetPrediction, PharmMapper, SuperPRED, and TargetNet were used to predict the Osthole targets. GeneCards and the OMIM database were used to indicate bladder cancer targets. The intersection of two target gene fragments was used to obtain the key target genes. Protein–protein interaction (PPI) analysis was performed using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Furthermore, we used gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to explore the molecular function of target genes. AutoDock software was then used to perform molecular docking of target genes,osthole and co-crystal ligand. Finally, an in vitro experiment was conducted to validate bladder cancer inhibition by osthole. Results Our analysis identified 369 intersection genes for osthole, the top ten target genes included MAPK1, AKT1, SRC, HRAS, HASP90AA1, PIK3R1, PTPN11, MAPK14, CREBBP, and RXRA. The GO and KEGG pathway enrichment results revealed that the PI3K-AKT pathway was closely correlated with osthole against bladder cancer. The osthole had cytotoxic effect on bladder cancer cells according to the cytotoxic assay. Additionally, osthole blocked the bladder cancer epithelial-mesenchymal transition and promoted bladder cancer cell apoptosis by inhibiting the PI3K-AKT and Janus kinase/signal transducer and activator of transcription (JAK/STAT3) pathways. Conclusions We found that osthole had cytotoxic effect on bladder cancer cells and inhibited invasion, migration, and epithelial-mesenchymal transition by inhibiting PI3K-AKT and JAK/STAT3 pathways in in vitro experiment. Above all, osthole might have potential significance in treatment of bladder cancer. Subjects Bioinformatics, Computational Biology, Molecular Biology.

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Section: Methodsmentioning

confidence: 99%

Potential mechanisms of osthole against bladder cancer cells based on network pharmacology, molecular docking, and experimental validation

Jiang

Zhang

Wang

et al. 2023

BMC Complement Med Ther

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“…A PDB file containing data to create 3D rendering of the wild type NHLH2 protein was obtained from AlphaFold Protein Structure Database (European Molecular Biology Laboratory, Cambridge, UK) [ 46 , 47 ]. The data contained in the PDB file was uploaded into pyMOL (Schrodinger, Inc, New Yori, NY, USA) [ 48 ], a molecular visualization platform, to view the location of the 22 SNVs of interest listed in Table 1 . Amino acid positions highlighted in yellow denote positions of variants that allow for DNA interaction that appears altered by FunFold2.…”

Section: Methodsmentioning

confidence: 99%

In Silico Examination of Single Nucleotide Missense Mutations in NHLH2, a Gene Linked to Infertility and Obesity

Madsen

Good

2023

IJMS

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Continual advances in our understanding of the human genome have led to exponential increases in known single nucleotide variants. The characterization of each of the variants lags behind. For researchers needing to study a single gene, or multiple genes in a pathway, there must be ways to narrow down pathogenic variants from those that are silent or pose less pathogenicity. In this study, we use the NHLH2 gene which encodes the nescient helix-loop-helix 2 (Nhlh2) transcription factor in a systematic analysis of all missense mutations to date in the gene. The NHLH2 gene was first described in 1992. Knockout mice created in 1997 indicated a role for this protein in body weight control, puberty, and fertility, as well as the motivation for sex and exercise. Only recently have human carriers of NHLH2 missense variants been characterized. Over 300 missense variants for the NHLH2 gene are listed in the NCBI single nucleotide polymorphism database (dbSNP). Using in silico tools, predicted pathogenicity of the variants narrowed the missense variants to 37 which were predicted to affect NHLH2 function. These 37 variants cluster around the basic-helix-loop-helix and DNA binding domains of the transcription factor, and further analysis using in silico tools provided 21 SNV resulting in 22 amino acid changes for future wet lab analysis. The tools used, findings, and predictions for the variants are discussed considering the known function of the NHLH2 transcription factor. Overall use of these in silico tools and analysis of these data contribute to our knowledge of a protein which is both involved in the human genetic syndrome, Prader–Willi syndrome, and in controlling genes involved in body weight control, fertility, puberty, and behavior in the general population, and may provide a systematic methodology for others to characterize variants for their gene of interest.

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“…The mutation process of structures of the 19 site-saturation mutants was executed based on the wild-type PentS–FPP complex with the Mutagenesis Wizard tool of PyMol software [ 21 ]. At least 10 ns MD simulations for each mutant were performed using Amber20 software to gain insight into the thermodynamic and structural details of mutation-linked tertiary changes [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

A Single Active-Site Mutagenesis Confers Enhanced Activity and/or Changed Product Distribution to a Pentalenene Synthase from Streptomyces sp. PSKA01

et al. 2023

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Pentalenene is a ternary cyclic sesquiterpene formed via the ionization and cyclization of farnesyl pyrophosphate (FPP), which is catalyzed by pentalenene synthase (PentS). To better understand the cyclization reactions, it is necessary to identify more key sites and elucidate their roles in terms of catalytic activity and product specificity control. Previous studies primarily relied on the crystal structure of PentS to analyze and verify critical active sites in the active cavity, while this study started with the function of PentS and screened a novel key site through random mutagenesis. In this study, we constructed a pentalenene synthetic pathway in E. coli BL21(DE3) and generated PentS variants with random mutations to construct a mutant library. A mutant, PentS-13, with a varied product diversity, was obtained through shake-flask fermentation and product identification. After sequencing and the functional verification of the mutation sites, it was found that T182A, located in the G2 helix, was responsible for the phenotype of PentS-13. The site-saturation mutagenesis of T182 demonstrated that mutations at this site not only affected the solubility and activity of the enzyme but also affected the specificity of the product. The other products were generated through different routes and via different carbocation intermediates, indicating that the 182 active site is crucial for PentS to stabilize and guide the regioselectivity of carbocations. Molecular docking and molecular dynamics simulations suggested that these mutations may induce changes in the shape and volume of the active cavity and disturb hydrophobic/polar interactions that were sufficient to reposition reactive intermediates for alternative reaction pathways. This article provides rational explanations for these findings, which may generally allow for the protein engineering of other terpene synthases to improve their catalytic efficiency or modify their specificities.

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Boosting the Full Potential of PyMOL with Structural Biology Plugins

Cited by 54 publications

References 104 publications

Potential mechanisms of osthole against bladder cancer cells based on network pharmacology, molecular docking, and experimental validation

Potential mechanisms of osthole against bladder cancer cells based on network pharmacology, molecular docking, and experimental validation

In Silico Examination of Single Nucleotide Missense Mutations in NHLH2, a Gene Linked to Infertility and Obesity

A Single Active-Site Mutagenesis Confers Enhanced Activity and/or Changed Product Distribution to a Pentalenene Synthase from Streptomyces sp. PSKA01

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