scholarly journals Virtual screening of integrase inhibitors by large scale binding free energy calculations: the SAMPL4 challenge

2014 ◽  
Vol 28 (4) ◽  
pp. 475-490 ◽  
Author(s):  
Emilio Gallicchio ◽  
Nanjie Deng ◽  
Peng He ◽  
Lauren Wickstrom ◽  
Alexander L. Perryman ◽  
...  
Keyword(s):  
Free Energy ◽  
Virtual Screening ◽  
Large Scale ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Integrase Inhibitors ◽  
Energy Calculations ◽  
Binding Free Energy Calculations

Large-Scale Assessment of Binding Free Energy Calculations in Active Drug Discovery Projects

2020 ◽  
Vol 60 (11) ◽  
pp. 5457-5474 ◽  
Author(s):  
Christina E. M. Schindler ◽  
Hannah Baumann ◽  
Andreas Blum ◽  
Dietrich Böse ◽  
Hans-Peter Buchstaller ◽  
...  
Keyword(s):  
Free Energy ◽  
Drug Discovery ◽  
Large Scale ◽  
Active Drug ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Energy Calculations ◽  
Large Scale Assessment ◽  
Scale Assessment ◽  
Binding Free Energy Calculations

Binding free energy calculations and biological testing of novel thiobarbiturates as inhibitors of the human NAD+ dependent histone deacetylase Sirt2

MedChemComm ◽  
2012 ◽  
Vol 3 (2) ◽  
pp. 167-173 ◽  
Author(s):  
Urszula Uciechowska ◽  
Jörg Schemies ◽  
Michael Scharfe ◽  
Michael Lawson ◽  
Kanin Wichapong ◽  
...  
Keyword(s):  
Free Energy ◽  
Virtual Screening ◽  
Histone Deacetylase ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Biological Testing ◽  
Energy Calculations ◽  
Binding Free Energy Calculations

Novel thiobarbiturates were identified by virtual screening and MM-PBSA calculation as potent sirtuin inhibitors which represent useful probes for cellular studies.

scholarly journals Structure-Based Virtual Screening, Molecular Dynamics and Binding Free Energy Calculations of Hit Candidates as ALK-5 Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 264
Author(s):  
Sheila C. Araujo ◽  
Vinicius G. Maltarollo ◽  
Michell O. Almeida ◽  
Leonardo L. G. Ferreira ◽  
Adriano D. Andricopulo ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Virtual Screening ◽  
Anticancer Agents ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Energy Calculations ◽  
Cellular Events ◽  
Binding Free Energy Calculations ◽  
Alk 5

Activin-like kinase 5 (ALK-5) is involved in the physiopathology of several conditions, such as pancreatic carcinoma, cervical cancer and liver hepatoma. Cellular events that are landmarks of tumorigenesis, such as loss of cell polarity and acquisition of motile properties and mesenchymal phenotype, are associated to deregulated ALK-5 signaling. ALK-5 inhibitors, such as SB505154, GW6604, SD208, and LY2157299, have recently been reported to inhibit ALK-5 autophosphorylation and induce the transcription of matrix genes. Due to their ability to impair cell migration, invasion and metastasis, ALK-5 inhibitors have been explored as worthwhile hits as anticancer agents. This work reports the development of a structure-based virtual screening (SBVS) protocol aimed to prospect promising hits for further studies as novel ALK-5 inhibitors. From a lead-like subset of purchasable compounds, five molecules were identified as putative ALK-5 inhibitors. In addition, molecular dynamics and binding free energy calculations combined with pharmacokinetics and toxicity profiling demonstrated the suitability of these compounds to be further investigated as novel ALK-5 inhibitors.

Large-Scale Assessment of Binding Free Energy Calculations in Active Drug Discovery Projects

2020 ◽  
Author(s):  
Christina Schindler ◽  
Hannah Baumann ◽  
Andreas Blum ◽  
Dietrich Böse ◽  
Hans-Peter Buchstaller ◽  
...  
Keyword(s):  
Free Energy ◽  
Drug Discovery ◽  
Large Scale ◽  
Active Drug ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Energy Calculation ◽  
Large Scale Assessment ◽  
New Public ◽  
Binding Free Energy Calculations

Here we present an evaluation of the binding affinity prediction accuracy of the free energy calculation method FEP+ on internal active drug discovery projects and on a large new public benchmark set.<br>

scholarly journals Automation of absolute protein-ligand binding free energy calculations for docking refinement and compound evaluation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Germano Heinzelmann ◽  
Michael K. Gilson
Keyword(s):  
Free Energy ◽  
Early Stage ◽  
Binding Free Energy ◽  
Low Cost ◽  
Free Energy Calculations ◽  
Free Energies ◽  
Energy Calculations ◽  
Drug Candidates ◽  
Binding Free Energy Calculations ◽  
Binding Free Energies

AbstractAbsolute binding free energy calculations with explicit solvent molecular simulations can provide estimates of protein-ligand affinities, and thus reduce the time and costs needed to find new drug candidates. However, these calculations can be complex to implement and perform. Here, we introduce the software BAT.py, a Python tool that invokes the AMBER simulation package to automate the calculation of binding free energies for a protein with a series of ligands. The software supports the attach-pull-release (APR) and double decoupling (DD) binding free energy methods, as well as the simultaneous decoupling-recoupling (SDR) method, a variant of double decoupling that avoids numerical artifacts associated with charged ligands. We report encouraging initial test applications of this software both to re-rank docked poses and to estimate overall binding free energies. We also show that it is practical to carry out these calculations cheaply by using graphical processing units in common machines that can be built for this purpose. The combination of automation and low cost positions this procedure to be applied in a relatively high-throughput mode and thus stands to enable new applications in early-stage drug discovery.

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