Phosphorylation Modification Force Field FB18CMAP Improving Conformation Sampling of Phosphoproteins

Song, Ge; Zhong, Bozitao; Zhang, Bo; Rehman, Ashfaq Ur; Chen, Hai-Feng

doi:10.1021/acs.jcim.3c00112

Cited by 9 publications

(7 citation statements)

References 70 publications

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“…Molecular docking simulations were performed to identify the putative targets of AQQ2 and AQQ7 . As AQQ2 and AQQ7 have shown activity against breast, cervical, and prostate cancer cell lines, we selected three proteins: cyclooxygenase (COX, PDB:6BL4), phosphate and tensin homolog (PTEN, PDB:1D5R), and epidermal growth factor receptor (EGFR, PDB:1M17), which have been reported to be overexpressed in these cancers (Gonzalez‐Conchas et al, 2018; Harris et al, 2014; Hirsch et al, 2003; Song et al, 2023). Table 5 summarizes the results of docking simulations.…”

Section: Resultsmentioning

confidence: 99%

Cytotoxic activity of quinolinequinones in cancer: In vitro studies, molecular docking, and ADME/PK profiling

et al. 2023

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Lead molecules containing 1,4‐quinone moiety are intriguing novel compounds that can be utilized to treat cancer owing to their antiproliferative activities. Nine previously reported quinolinequinones (AQQ1‐9) were studied to better understand their inhibitory profile to produce potent and possibly safe lead molecules. The National Cancer Institute (NCI) of Bethesda chose all quinolinequinones (AQQ1‐9) based on the NCI Developmental Therapeutics Program and tested them against a panel of 60 cancer cell lines. At a single dose and five further doses, AQQ7 significantly inhibited the proliferation of all leukemia cell lines and some breast cancer cell lines. We investigated the in vitro cytotoxic activities of the most promising compounds, AQQ2 and AQQ7, in MCF7 and T‐47D breast cancer cells, DU‐145 prostate cancer cells, HCT‐116 and COLO 205 colon cancer cell lines, and HaCaT human keratinocytes using the MTT assay. AQQ7 showed particularly high cytotoxicity against MCF7 cells. Further analysis showed that AQQ7 exhibits anticancer activity through the induction of apoptosis without causing cell cycle arrest or oxidative stress. Molecular docking simulations for AQQ2 and AQQ7 were conducted against the COX, PTEN, and EGFR proteins, which are commonly overexpressed in breast, cervical, and prostate cancers. The in vitro ADME and in vivo PK profiling of these compounds have also been reported.

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Section: Resultsmentioning

confidence: 99%

Cytotoxic activity of quinolinequinones in cancer: In vitro studies, molecular docking, and ADME/PK profiling

et al. 2023

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“…The analysis on structural properties reveals a strong preference in structured and helicesabundant proteins, preventing them to generate much coil regions and intrinsically disordered proteins. These proteins are currently studied through molecular dynamics (MD) simulation [85][86][87] or conformational sampling 88 , which are discarded from most hand-picked training sets of protein backbone generation methods aiming to improve the fitness of models. An example of these tasks is the design of non-idealized proteins attempting to deal with the aforementioned preferences of current methods, which has seen progress in 89 .…”

Section: Discussionmentioning

confidence: 99%

A Unified Framework of Scaffold-Lab for Critical Assessment of Protein Backbone Generation Methods

chen,

Zheng,

Zhang

et al. 2024

Preprint

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De novo protein design has undergone a rapid development in recent years, especially for backbone generation, which stands out as more challenging yet valuable, offering the ability to design novel protein folds with fewer constraints. However, a comprehensive delineation of its potential for practical application in protein engineering remains lacking, as does a standardized evaluation framework to accurately assess the diverse methodologies within this field. Here, we proposed Scaffold-Lab benchmark focusing on evaluating unconditional generation across metrics like designability, novelty, diversity, efficiency and structural properties. We also extrapolated our benchmark to include the motif-scaffolding problem, demonstrating the utility of these conditional generation models. Our findings reveal that FrameFlow and RFdiffusion in unconditional generation and GPDL-H in conditional generation showcased the most outstanding performances. Furthermore, we described a systematic study to investigate conditional generation and applied it to the motif-scaffolding task, offering a novel perspective for the analysis and development of conditional protein design methods. All data and scripts are available at https://github.com/Immortals-33/Scaffold-Lab.

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“…The analysis on structural properties reveals a strong preference in structured and helicesabundant proteins, preventing them to generate much coil regions and intrinsically disordered proteins. These proteins are currently studied through molecular dynamics (MD) simulation [88][89][90] or conformational sampling 91 , which are discarded from most hand-picked training sets of protein backbone generation methods aiming to improve the fitness of models. An example of these tasks is the design of non-idealized proteins attempting to deal with the aforementioned preferences of current methods, which has seen progress in 92 .…”

Section: Discussionmentioning

confidence: 99%

Scaffold-Lab: Critical Evaluation and Ranking of Protein Backbone Generation Methods in A Unified Framework

Zheng,

Zhang,

Zhong

et al. 2024

Preprint

Self Cite

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De novo protein design has undergone a rapid development in recent years, particularly in fix-backbone sequence design and backbone generation. The latter stands out as more challenging yet valuable, offering the ability to design novel protein folds with fewer constraints. However, there is an absence of a comprehensive delineation of its potential for integration into practical applications in the field of protein engineering, as well as a standardized evaluation framework to accurately assess the diverse methodologies within this field. Here, we proposed Scaffold-Lab benchmark focusing on evaluating unconditional generation across metrics such as designability, novelty, diversity, efficiency and structural properties. We also extend our benchmark to include the motif-scaffolding problem, demonstrating the applicability of these conditional generation models. Our findings reveal that FrameFlow and RFdiffusion in unconditional generation and GPDL in conditional generation showcased the most outstanding performances. All data and script will be available at https://github.com/Immortals-33/Scaffold-Lab.

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Phosphorylation Modification Force Field FB18CMAP Improving Conformation Sampling of Phosphoproteins

Cited by 9 publications

References 70 publications

Cytotoxic activity of quinolinequinones in cancer: In vitro studies, molecular docking, and ADME/PK profiling

Cytotoxic activity of quinolinequinones in cancer: In vitro studies, molecular docking, and ADME/PK profiling

A Unified Framework of Scaffold-Lab for Critical Assessment of Protein Backbone Generation Methods

Scaffold-Lab: Critical Evaluation and Ranking of Protein Backbone Generation Methods in A Unified Framework

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