Kinases and phosphatases最新文献_第3页

Recent Advancements in Computational Drug Design Algorithms through Machine Learning and Optimization 基于机器学习和优化的计算药物设计算法的最新进展

Kinases and phosphatases Pub Date : 2023-05-05 DOI: 10.3390/kinasesphosphatases1020008

Soham Choudhuri, Manas Yendluri, Sudip Poddar, Aimin Li, Koushik Mallick, Saurav Mallik, B. Ghosh

{"title":"Recent Advancements in Computational Drug Design Algorithms through Machine Learning and Optimization","authors":"Soham Choudhuri, Manas Yendluri, Sudip Poddar, Aimin Li, Koushik Mallick, Saurav Mallik, B. Ghosh","doi":"10.3390/kinasesphosphatases1020008","DOIUrl":"https://doi.org/10.3390/kinasesphosphatases1020008","url":null,"abstract":"The goal of drug discovery is to uncover new molecules with specific chemical properties that can be used to cure diseases. With the accessibility of machine learning techniques, the approach used in this search has become a significant component in computer science in recent years. To meet the Precision Medicine Initiative’s goals and the additional obstacles that they have created, it is vital to develop strong, consistent, and repeatable computational approaches. Predictive models based on machine learning are becoming increasingly crucial in preclinical investigations. In discovering novel pharmaceuticals, this step substantially reduces expenses and research times. The human kinome contains various kinase enzymes that play vital roles through catalyzing protein phosphorylation. Interestingly, the dysregulation of kinases causes various human diseases, viz., cancer, cardiovascular disease, and several neuro-degenerative disorders. Thus, inhibitors of specific kinases can treat those diseases through blocking their activity as well as restoring normal cellular signaling. This review article discusses recent advancements in computational drug design algorithms through machine learning and deep learning and the computational drug design of kinase enzymes. Analyzing the current state-of-the-art in this sector will offer us a sense of where cheminformatics may evolve in the near future and the limitations and beneficial outcomes it has produced. The approaches utilized to model molecular data, the biological problems addressed, and the machine learning algorithms employed for drug discovery in recent years will be the emphasis of this review.","PeriodicalId":74042,"journal":{"name":"Kinases and phosphatases","volume":"20 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72436002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Regulation of Ras-GTPase Signaling and Localization by Post-Translational Modifications 翻译后修饰对Ras-GTPase信号转导和定位的调控

Kinases and phosphatases Pub Date : 2023-04-21 DOI: 10.3390/kinasesphosphatases1020007

A. Nair, Bhaskar Saha

{"title":"Regulation of Ras-GTPase Signaling and Localization by Post-Translational Modifications","authors":"A. Nair, Bhaskar Saha","doi":"10.3390/kinasesphosphatases1020007","DOIUrl":"https://doi.org/10.3390/kinasesphosphatases1020007","url":null,"abstract":"Ras, a GTP-GDP binary switch protein, transduces signals from diverse receptors to regulate various signaling networks. Three Ras genes encode for protein isoforms, namely, Harvey Ras (H-Ras), Kirsten Ras (K-Ras, with two splice variants, K-Ras4A and K-Ras4B), and Neuroblastoma Ras (N-Ras). The isoforms undergo a series of post-translational modifications that enable their membrane attachment and biological activity. The activation of Ras isoforms is tightly regulated, and any dysregulation affects cellular processes, such as cell division, apoptosis, differentiation, cell migration, etc. The Ras gene is highly prone to mutation, and ~30% of cancers carry somatic mutations in Ras, whereas germline mutations clinically manifest as various rasopathies. In addition to regulation by the Guanine nucleotide exchange factors and the GTPase activation proteins, Ras signaling, and localization are also regulated by phosphorylation-dephosphorylation, ubiquitination, nitrosylation, and acetylation. Herein, we review the regulation of Ras signaling and localization by various regulatory enzymes in depth and assess the current status of Ras drug discovery targeting these regulatory enzymes.","PeriodicalId":74042,"journal":{"name":"Kinases and phosphatases","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80318743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Therapeutic Perspectives on ROCK Inhibition for Cerebral Cavernous Malformations ROCK抑制脑海绵状血管瘤的治疗前景

Kinases and phosphatases Pub Date : 2023-02-23 DOI: 10.3390/kinasesphosphatases1010006

T. Montagnoli, D. R. D. de OLIVEIRA, C. A. Fraga

引用次数: 1

Site-Specific Phosphorylation of RTK KIT Kinase Insert Domain: Interactome Landscape Perspectives RTK KIT激酶插入结构域的位点特异性磷酸化:相互作用组景观视角

Kinases and phosphatases Pub Date : 2023-02-15 DOI: 10.3390/kinasesphosphatases1010005

Julie Ledoux, L. Tchertanov

{"title":"Site-Specific Phosphorylation of RTK KIT Kinase Insert Domain: Interactome Landscape Perspectives","authors":"Julie Ledoux, L. Tchertanov","doi":"10.3390/kinasesphosphatases1010005","DOIUrl":"https://doi.org/10.3390/kinasesphosphatases1010005","url":null,"abstract":"The kinase insert domain (KID) of RTK KIT is a key recruitment region for downstream signalling proteins (DSPs). KID, as a multisite phosphorylation region, provides alternative recognition sites for DSPs and activates them by binding a phosphotyrosine (pY) to their SH2 domains. Significant steric, biochemical, and biophysical requirements must be fulfilled by each pair of interacting proteins as the adaptation of their configurations is mandatory for the selective activation of DSPs. The accurate 3D atomistic models obtained by modelling and molecular dynamics (MD) simulations of phosphorylated KID (p-KID) have been delivered to describe KID INTERACTOME. By taking phosphorylated KIDpY721 and the N-terminal SH2 domain of phosphatidylinositol 3-kinase (PI3K), a physiological partner of KID, we showed the two proteins are intrinsically disordered. Using 3D models of both proteins, we probe alternative orientations of KIDpY721 relative to the SH2 binding pocket using automatic docking (HADDOCK) and intuitive user-guided docking. This modelling yields to two possible models of the functionally related non-covalent complex KIDpY721/SH2, where one can be regarded as the first precursor to probe PI3K activation via KIT KID. We suggest that such generation of a KID/SH2 complex is best suited for future studies of the post-transduction effects of RTK KIT.","PeriodicalId":74042,"journal":{"name":"Kinases and phosphatases","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82132111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Stress Hub in Scedosporium apiospermum: The High Osmolarity Glycerol (HOG) Pathway 高渗透压甘油(HOG)途径:高渗透压甘油(HOG)途径

Kinases and phosphatases Pub Date : 2022-11-21 DOI: 10.3390/kinasesphosphatases1010002

Hajar Yaakoub, S. Mina, A. Marot, N. Papon, A. Calenda, J. Bouchara

{"title":"A Stress Hub in Scedosporium apiospermum: The High Osmolarity Glycerol (HOG) Pathway","authors":"Hajar Yaakoub, S. Mina, A. Marot, N. Papon, A. Calenda, J. Bouchara","doi":"10.3390/kinasesphosphatases1010002","DOIUrl":"https://doi.org/10.3390/kinasesphosphatases1010002","url":null,"abstract":"Scedosporium species are opportunistic filamentous fungi found in human-impacted areas. Clinically relevant species, such as S. apiospermum, rank as the second most frequent colonizers of the airways of patients with cystic fibrosis (CF), which are characterized by persistent oxidative stress. This raises the question of how Scedosporium species abate conditions imposed in hostile environments. Since the High Osmolarity Glycerol (HOG) pathway plays a central role in fungal adaptation to stress, we aimed to pheno-profile the involvement of the pathway in response to stress in S. apiospermum using Western blot. We show for the first time that a wide range of stress distinctively activates the HOG pathway in S. apiospermum, including oxidants (H2O2, menadione, cumene hydroperoxide, diamide, paraquat, and honokiol), osmotic agents (sorbitol and KCl), cell-wall stress agents (caffeine, calcofluor white, and Congo Red), heavy metals (cadmium and arsenite), fungicides (fludioxonil and iprodione), antifungals (voriconazole and amphotericin B), and acid stress (pH 4). We suggest that the function of the HOG pathway as a general stress regulator is also conserved in S. apiospermum.","PeriodicalId":74042,"journal":{"name":"Kinases and phosphatases","volume":"99 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90392291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Kinases and Phosphatases: The Challenge of a New Journal Entirely Focused on Post-Translational Modifications 激酶和磷酸酶:一个完全专注于翻译后修饰的新期刊的挑战

Kinases and phosphatases Pub Date : 2022-10-12 DOI: 10.3390/kinasesphosphatases1010001

M. Salvi

引用次数: 0