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Alloscore: a method for predicting allosteric ligand–protein interactions

Shuai Li, Qiancheng Shen, Minyi Su, Xinyi Liu, Shaoyong Lu, Zhongjie Chen, Renxiao Wang, Jian Zhang
2016 Bioinformatics  
Herein, we introduce Alloscore, a web server that predicts the binding affinities of allosteric ligand-protein interactions.  ...  Despite the great interest in the development of allosteric drugs as a new tactic in drug discovery, the understanding of the ligand-protein interactions underlying allosteric binding represents a key  ...  In this study, we introduce Alloscore, a web server that predicts the binding affinities of allosteric ligand-protein interactions, for the first time.  ... 
doi:10.1093/bioinformatics/btw036 pmid:26803160 fatcat:pjonoiqxubdiri7e7huqbknhdy

AlloFinder: a strategy for allosteric modulator discovery and allosterome analyses

Min Huang, Kun Song, Xinyi Liu, Shaoyong Lu, Qiancheng Shen, Renxiao Wang, Jingze Gao, Yuanyuan Hong, Qian Li, Duan Ni, Jianrong Xu, Guoqiang Chen (+1 others)
2018 Nucleic Acids Research  
Characterizing the potential allosteric metabolite-protein interactions by screening the library may thus deepen our understanding of the molecular underpinnings for metabolites in feedback modulation  ...  We built the algorithm in the AlloFinder server and a parameter of ten thousand iterations in pocket detection is used to obtain more accurate pockets throughout a query protein.  ...  the AlloFinder server), which is specifically designed for accurate allosteric modulator-protein interaction evaluation and outperforms other methods in the prediction of allosteric modulator-protein  ... 
doi:10.1093/nar/gky374 pmid:29757429 pmcid:PMC6030990 fatcat:zhadun33gjefrcjj5qn7pnrxci

Identification and Biological Evaluation of CK2 Allosteric Fragments through Structure-Based Virtual Screening

Chunqiong Li, Xuewen Zhang, Na Zhang, Yue Zhou, Guohui Sun, Lijiao Zhao, Rugang Zhong
2020 Molecules  
Six hits forming the holistic interaction mechanism with the αD pocket were retained after pharmacophore- and Alloscore-based screening for biological test.  ...  The ChemBridge fragment library was searched by evaluating the fit values of these molecules with the optimized pharmacophore model, as well as the binding affinity of the CK2α-ligand complexes predicted  ...  Alloscore is a web server that predicts the binding affinities of allosteric ligand-protein interactions.  ... 
doi:10.3390/molecules25010237 pmid:31935979 fatcat:zbk7nlayyrefhiohxgx2275vuu

Unraveling allosteric landscapes of allosterome with ASD

2019 Nucleic Acids Research  
Allosteric regulation is one of the most direct and efficient ways to fine-tune protein function; it is induced by the binding of a ligand at an allosteric site that is topographically distinct from an  ...  To facilitate research from the perspective of the allosterome, in ASD 2019, novel features were curated as follows: (i) >10 000 potential allosteric sites of human proteins were deposited for allosteric  ...  As a supplement to experimental methods, computational predictions of allosteric sites in proteins made using the ASD data can expedite allosteric drug discovery.  ... 
doi:10.1093/nar/gkz958 pmid:31665428 pmcid:PMC7145546 fatcat:5fmt4tq7rfbinolrvvccvn2vqi

Integrated Computational Approaches and Tools for Allosteric Drug Discovery

Sheik Amamuddy, Veldman, Manyumwa, Khairallah, Agajanian, Oluyemi, Verkhivker, Tastan Bishop
2020 International Journal of Molecular Sciences  
The proliferation of novel computational approaches for predictingligand–protein interactions and binding using dynamic and network-centric perspectives has ledto new insights into allosteric mechanisms  ...  Although no absolute method of experimental and in silico allosteric drug/site discoveryexists, current methods are still being improved.  ...  Alloscore [222] Uses a linear combination of non-bonded interaction terms, a deformation term and geometric features to predict the binding affinities of protein-ligand interactions.  ... 
doi:10.3390/ijms21030847 pmid:32013012 pmcid:PMC7036869 fatcat:y2z5vnsylnduhc7gntjkpcoslq

Recent Advances in the Discovery of CK2 Allosteric Inhibitors: From Traditional Screening to Structure-Based Design

Xiaolan Chen, Chunqiong Li, Dada Wang, Yu Chen, Na Zhang
2020 Molecules  
This study is expected to provide valuable clues for the design of CK2 allosteric inhibitors.  ...  Traditional serendipitous screening and structure-based design are robust tools for the discovery of CK2 allosteric inhibitors.  ...  We classified these inhibitors according to the allosteric sites where they bind, including Sites 1,2 and 3, and presented their discovery method and the key receptor-ligand interactions at the allosteric  ... 
doi:10.3390/molecules25040870 pmid:32079098 pmcid:PMC7070378 fatcat:4fscqu4gtbhg3l6lqebrueg2wu

Investigation of an Allosteric Deoxyhypusine Synthase Inhibitor in P. falciparum

Aiyada Aroonsri, Chayaphat Wongsombat, Philip Shaw, Siegrid Franke, Jude Przyborski, Annette Kaiser
2022 Molecules  
Virtual screening of the allosteric database identified candidate ligand binding to novel binding pockets identified in P. falciparum dhs, which might foster the development of parasite-specific inhibitors  ...  Recently, the synthesis of a series of human dhs inhibitors led to 6-bromo-N-(1H-indol-4yl)-1-benzothiophene-2-carboxamide, a potent allosteric inhibitor with an IC50 value of 0.062 µM.  ...  Tsikas, Institute of Clinical Pharmacology, Hannover Medical School, for his scientific advice. Conflicts of Interest: The authors declare no conflict of interest.  ... 
doi:10.3390/molecules27082463 pmid:35458660 pmcid:PMC9030622 fatcat:rza3mti2mzfmdla2yuykh5uwsu

Are there physicochemical differences between allosteric and competitive ligands?

Richard D. Smith, Jing Lu, Heather A. Carlson, Elena Papaleo
2017 PLoS Computational Biology  
Competitive ligands bind in the active site of a protein while allosteric ligands exhibit their effect from a remote location on the protein.  ...  This dataset contains 70,219 and 9,511 unique ligands for the allosteric and competitive sets, respectively.  ...  Acknowledgments We would like to thank the Chemical Computing Group for their generous donation of the MOE software package for this research. Author Contributions  ... 
doi:10.1371/journal.pcbi.1005813 pmid:29125840 pmcid:PMC5699844 fatcat:lnszd5q5yfh3rdnain2rtfgqmq

Rational design of allosteric modulators: challenges and successes

Alexios Chatzigoulas, Zoe Cournia
2021 Zenodo  
We also illustrate representative studies for allosteric modulators design for proteins belonging to a wide range of protein families, also considering irreversible binding with covalent allosteric modulators  ...  as a new avenue for drug discovery.  ...  Compounds were ranked by a binding scoring method for affinity prediction of allosteric ligand-protein interactions, Alloscore. 187 The top 15 hits were assayed, with one compound inhibiting STAT3.  ... 
doi:10.5281/zenodo.4889093 fatcat:4o3cx7wrgja35dvjfbmjoac4v4

In silico Methods for Design of Kinase Inhibitors as Anticancer Drugs

Zarko Gagic, Dusan Ruzic, Nemanja Djokovic, Teodora Djikic, Katarina Nikolic
2020 Frontiers in Chemistry  
interaction with the drug target, and design more efficient drug candidates.  ...  In this review, computational methods used in rational drug design of kinase inhibitors are discussed and compared, considering some representative case studies.  ...  In 2011, Buchwald et al. used SVM to prepare the model for prediction of protein kinases-ligand interactions.  ... 
doi:10.3389/fchem.2019.00873 pmid:31970149 pmcid:PMC6960140 fatcat:725g6v22hfhgniplq2xdlxed4m

Drugging Ras GTPase: a comprehensive mechanistic and signaling structural view

Shaoyong Lu, Hyunbum Jang, Shuo Gu, Jian Zhang, Ruth Nussinov
2016 Chemical Society Reviews  
approaches for predicting allosteric sites (Allosite, Alloscore and ASBench), and the identification of allosteric modulators for proteins.  ...  Three different approaches for the identification of potential binding sites, including fragment, grid, and ligand based bindingsite mapping methods, were subsequently performed on the ensemble of Ras  ... 
doi:10.1039/c5cs00911a pmid:27396271 pmcid:PMC5021603 fatcat:m75d6w2gq5hafezho3jzflekju