Inside the Hsp90 inhibitors binding mode through induced fit docking

Lauria, Antonino; Ippolito, Mario; Almerico, Anna Maria

doi:10.1016/j.jmgm.2008.11.004

Cited by 29 publications

(19 citation statements)

References 35 publications

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“…Schrodinger's Induced Fit Docking (IFD) Workflow (23,24) involves rigid receptor docking with Glide (25,26), combined with protein-ligand complex minimization with the homology modeling module Prime (24). IFD has been successfully used for studies of kinases (27,28), HIV-1 Integrase (29), heat shock protein 90 (30), monoacylglycerol lipase (31).…”

Section: Receptor Flexibility By Monte Carlo (Mc) Simulations and Rotmentioning

confidence: 99%

Challenges and advances in computational docking: 2009 in review

Yuriev

Agostino

Ramsland

2010

J of Molecular Recognition

306

196

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Docking is a computational technique that places a small molecule (ligand) in the binding site of its macromolecular target (receptor) and estimates its binding affinity. This review addresses methodological developments that have occurred in the docking field in 2009, with a particular focus on the more difficult, and sometimes controversial, aspects of this promising computational discipline. These developments aim to address the main challenges of docking: receptor representation (such aspects as structural waters, side chain protonation, and, most of all, flexibility (from side chain rotation to domain movement)), ligand representation (protonation, tautomerism and stereoisomerism, and the effect of input conformation), as well as accounting for solvation and entropy of binding. This review is strongly focused on docking advances in the context of drug design, specifically in virtual screening and fragment-based drug design.

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Section: Receptor Flexibility By Monte Carlo (Mc) Simulations and Rotmentioning

confidence: 99%

Challenges and advances in computational docking: 2009 in review

Yuriev

Agostino

Ramsland

2010

J of Molecular Recognition

306

196

View full text Add to dashboard Cite

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“…208–212 The engagement of a client protein with the HSP70/HSP40/HSP90 complex and p60 HOP forms the HSP90 multichaperone complex, in which functional conformation and activation of the client protein require the binding of ATP to the N-terminal domain of HSP90. 208,212–214 Several oncogenic proteins are regulated by HSP90, including c-kit, HER-2, FLT3, BCR-ABL, ZAP-70, Akt, NPM-ALK, Raf-1, and mutated TP53. 209,215–222 High HSP90 levels were identified in many solid tumors.…”

Section: Hsp90mentioning

confidence: 99%

Small molecule inhibitors in acute myeloid leukemia: from the bench to the clinic

Al-Hussaini

DiPersio

2014

Expert Review of Hematology

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Many patients with acute myeloid leukemia (AML) will eventually develop refractory or relapsed disease. In the absence of standard therapy for this population, there is currently an urgent unmet need for novel therapeutic agents. Targeted therapy with small molecule inhibitors (SMIs) represents a new therapeutic intervention that has been successful for the treatment of multiple tumors (e.g., gastrointestinal stromal tumors, chronic myelogenous leukemia). Hence, there has been great interest in generating selective small molecule inhibitors targeting critical pathways of proliferation and survival in AML. This review highlights a selective group of intriguing therapeutic agents and their presumed targets in both preclinical models and in early human clinical trials.

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“…This software generates information on the binding site's characteristics using novel search and analytical facilities: a SiteMap calculation begins with an initial search step which identifies or characterizes, through the use of a grid points, one or more regions on the protein surface that may be suitable for binding of ligands to the receptor. Then contour maps are generated, producing hydrophobic and hydrophilic maps (Lauria et al, 2009). The hydrophilic maps are further divided into donor, acceptor, and metal-binding regions.…”

Section: Active Site Predictionsmentioning

confidence: 99%

“…The hydrophilic maps are further divided into donor, acceptor, and metal-binding regions. The evaluation stage, which concludes the calculation, assesses each site by calculating various properties: number of site points, a measure of the site size; exposure/ enclosure, two properties providing different measures of how available is the site to the solvent; contact, which measures how strongly the average site point interacts with the surrounding receptor via van der Waals non-bonded interactions; donor/acceptor character, a property related to the sizes and intensities of H-donor and -acceptor regions; SiteScore, an overall property based on previous properties, constructed and calibrated so that the average SiteScore for a promising binding site is 1.0 (Lauria et al, 2009).…”

Section: Active Site Predictionsmentioning

confidence: 99%

Structure-based drug discovery of ApoE4 inhibitors from the plant compounds

et al. 2011

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Apolipoprotein E4 (ApoE4) is a potential target for developing new therapeutics for Alzheimer's disease (AD). Till now there is no drug available to inhibit this protein and cholinesterase inhibitor was given for almost all the AD patients. In this study, we have approached to identify the potential ApoE4 inhibitor from the plant compounds. Rigid docking study was performed for 18 plant compounds and 11 cholinesterase inhibitors. Based on the docking score, binding energy and number of hydrogen bonding curcumin posses the best scoring function. For further validation induce fit docking was performed and it also shows that curcumin binds to the same binding pocket of ApoE4 protein. Biological activity prediction reveals that curcumin has a potential therapeutic activity against AD. Pharmacokinetic properties of this compound are under the acceptable range. From the results we concluded that the plant compound curcumin could be a potential inhibitor of ApoE4 and it can control the AD.

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Inside the Hsp90 inhibitors binding mode through induced fit docking

Cited by 29 publications

References 35 publications

Challenges and advances in computational docking: 2009 in review

Challenges and advances in computational docking: 2009 in review

Small molecule inhibitors in acute myeloid leukemia: from the bench to the clinic

Structure-based drug discovery of ApoE4 inhibitors from the plant compounds

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