Combined free energy calculation and machine learning methods for understanding ligand unbinding kinetics

Autor: Magd Badaoui, Pedro J. Buigues, Dénes Berta, Gaurav M. Mandana, Hankang Gu, Tamás Földes, Callum J. Dickson, Viktor Hornak, Mitsunori Kato, Carla Molteni, Simon Parsons, Edina Rosta

Publikováno v: Journal of Chemical Theory and Computation
Badaoui, M, Buigues, P J, Berta, D, Mandana, G M, Gu, H, Földes, T, Dickson, C J, Hornak, V, Kato, M, Molteni, C, Parsons, S & Rosta, E 2022, ' Combined Free-Energy Calculation and Machine Learning Methods for Understanding Ligand Unbinding Kinetics ', Journal of Chemical Theory and Computation, vol. 18, no. 4, pp. 2543-2555 . https://doi.org/10.1021/acs.jctc.1c00924

The determination of drug residence times, which define the time an inhibitor is in complex with its target, is a fundamental part of the drug discovery process. Synthesis and experimental measurements of kinetic rate constants are, however, expensiv

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::080fe41a13ee1cbf063f1e1751bc2cf3

Modelling the active SARS-CoV-2 helicase complex as a basis for structure-based inhibitor design

Autor: Sarah A. Harris, Geoff Wells, Pedro J. Buigues, Magd Badaoui, Sam Alexander Martino, Andrei V. Pisliakov, Dénes Berta, Nadia Elghobashi-Meinhardt, Elisa Frezza, Edina Rosta

Publikováno v: Chemical Science
Chemical Science, The Royal Society of Chemistry, 2021, ⟨10.1039/D1SC02775A⟩

The RNA helicase (non-structural protein 13, NSP13) of SARS-CoV-2 is essential for viral replication, and it is highly conserved among the coronaviridae family, thus a prominent drug target to treat COVID-19. We present here structural models and dyn

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b08aa6f38118493fb3d11437378b7079
https://pubmed.ncbi.nlm.nih.gov/34777769

Cations in motion: QM/MM studies of the dynamic and electrostatic roles of H+ and Mg2+ ions in enzyme reactions

Autor: Edina Rosta, Magd Badaoui, Pedro J. Buigues, Dénes Berta

Publikováno v: Current Opinion in Structural Biology
Berta, D, Buigues, P J, Badaoui, M & Rosta, E 2020, ' Cations in motion: QM/MM studies of the dynamic and electrostatic roles of H + and Mg 2+ ions in enzyme reactions ', Current Opinion in Structural Biology, vol. 61, pp. 198-206 . https://doi.org/10.1016/j.sbi.2020.01.002

Here we discuss current trends in the simulations of enzymatic reactions focusing on phosphate catalysis. The mechanistic details of the proton transfers coupled to the phosphate cleavage is one of the key challenges in QM/MM calculations of these an

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53d87856099db56b5e49920259c261b6

Structural basis of second-generation HIV integrase inhibitor action and viral resistance

Autor: Wen Li, Allison Ballandras-Colas, Nicola J. Cook, Abhay Kotecha, Andrea Nans, Peter Cherepanov, Edina Rosta, Alan Engelman, Magd Badaoui, Dénes Berta

Publikováno v: Science
Cook, N J, Li, W, Berta, D, Badaoui, M, Ballandras-colas, A, Nans, A, Kotecha, A, Rosta, E, Engelman, A N & Cherepanov, P 2020, ' Structural basis of second-generation HIV integrase inhibitor action and viral resistance ', Science, vol. 367, no. 6479, pp. 806-810 . https://doi.org/10.1126/science.aay4919

Strengths and weaknesses of an HIV drug Retroviruses replicate by inserting a copy of their RNA, which has been reverse transcribed into DNA, into the host genome. This process involves the intasome, a nucleoprotein complex comprising copies of the v

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::861d0e60ed7c0b78ccbcdb5f89a032b5
https://pubmed.ncbi.nlm.nih.gov/32001525

Calculating Kinetic Rates and Membrane Permeability from Biased Simulations

Autor: Magd Badaoui, Carla Molteni, Viktor Hornak, Edina Rosta, Callum J. Dickson, Adam Kells

Publikováno v: Badaoui, M, Kells, A, Molteni, C, Dickson, C J, Hornak, V & Rosta, E 2018, ' Calculating Kinetic Rates and Membrane Permeability from Biased Simulation ', JOURNAL OF PHYSICAL CHEMISTRY B . https://doi.org/10.1021/acs.jpcb.8b07442

We present a simple approach to calculate the kinetic properties of lipid membrane crossing processes from biased molecular dynamics simulations. We demonstrate that by using biased simulations, one can obtain highly accurate kinetic information with

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2c90712c506e2861995d1c54eb98f452
https://pubmed.ncbi.nlm.nih.gov/30247032