From computer-aided drug discovery to computer-driven drug discovery

Autor: Sathesh Bhat, Leah L. Frye, Karen Akinsanya, Robert Abel

Publikováno v: Drug Discovery Today: Technologies. 39:111-117

Computational chemistry and structure-based design have traditionally been viewed as a subset of tools that could aid acceleration of the drug discovery process, but were not commonly regarded as a driving force in small molecule drug discovery. In t

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b7af5600222f4a6d2b0d683334b0337e
https://doi.org/10.1016/j.ddtec.2021.08.001

Accurate and Reliable Prediction of Relative Ligand Binding Potency in Prospective Drug Discovery by Way of a Modern Free-Energy Calculation Protocol and Force Field

Autor: Yuqing Deng, Edward Harder, Lingle Wang, Bruce J. Berne, Ramy Farid, Ron Wester, Richard A. Friesner, Levi C. T. Pierce, Teng-Yi Lin, Donna L. Romero, William L. Jorgensen, Mark L. Brewer, Murcko Mark A, Shaughnessy Robinson, Robert Abel, Jeremy R. Greenwood, Jennifer L. Knight, Thijs Beuming, Byungchan Kim, Goran Krilov, Leah L. Frye, Dmitry Lupyan, David L. Mobley, Wolfgang Damm, Yujie Wu, Thomas Steinbrecher, Craig E. Masse, Markus K. Dahlgren, Woody Sherman

Publikováno v: Journal of the American Chemical Society, vol 137, iss 7
Wang, L; Wu, Y; Deng, Y; Kim, B; Pierce, L; Krilov, G; et al.(2015). Accurate and reliable prediction of relative ligand binding potency in prospective drug discovery by way of a modern free-energy calculation protocol and force field. Journal of the American Chemical Society, 137(7), 2695-2703. doi: 10.1021/ja512751q. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/5061663w

© 2015 American Chemical Society. Designing tight-binding ligands is a primary objective of small-molecule drug discovery. Over the past few decades, free-energy calculations have benefited from improved force fields and sampling algorithms, as well

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::773d1836a8ebda0977ca7d9384d08fcb
https://doi.org/10.1021/ja512751q

Locating a plausible binding site for an open-channel blocker, GlyH-101, in the pore of the cystic fibrosis transmembrane conductance regulator

Autor: Mark S.P. Sansom, Leah L. Frye, Christopher Alexander, Nicolette O'Donnell, Anthony Ivetac, David C. Dawson, Yohei Norimatsu

High-throughput screening has led to the identification of small-molecule blockers of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, but the structural basis of blocker binding remains to be defined. We developed mol

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https://doi.org/10.1124/mol.112.080267

Epik: a software program for pK a prediction and protonation state generation for drug-like molecules

Autor: Leah L. Frye, Jeremy R. Greenwood, Makoto Uchimaya, Mathew R. Timlin, Anuradha Cholleti, John C. Shelley

Publikováno v: Journal of Computer-Aided Molecular Design. 21:681-691

Epik is a computer program for predicting pK(a) values for drug-like molecules. Epik can use this capability in combination with technology for tautomerization to adjust the protonation state of small drug-like molecules to automatically generate one

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https://doi.org/10.1007/s10822-007-9133-z

The design, synthesis and transmembrane transport studies of a biomimetic sterol-based ion channel

Autor: Herbert M. Schwartz, Leah L. Frye, John P. Fojtik, Carol A. Lisek, Anthony D. Pechulis, Richele J. Thompson

Publikováno v: Bioorganic & Medicinal Chemistry. 5:1893-1901

A model sterol-based ion channel was rationally designed and synthesized. The potential ion channel is comprised of a tartrate-derived crown ether to which six steroids are appended. Macromolecule 1a was incorporated into phospholipid vesicles and sh

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https://doi.org/10.1016/s0968-0896(97)00085-0