The transformational role of GPU computing and deep learning in drug discovery

M Pandey, M Fernandez, F Gentile, O Isayev… - Nature Machine …, 2022 - nature.com
Deep learning has disrupted nearly every field of research, including those of direct
importance to drug discovery, such as medicinal chemistry and pharmacology. This …

Cryo-EM in drug discovery: achievements, limitations and prospects

JP Renaud, A Chari, C Ciferri, W Liu… - Nature reviews Drug …, 2018 - nature.com
Cryo-electron microscopy (cryo-EM) of non-crystalline single particles is a biophysical
technique that can be used to determine the structure of biological macromolecules and …

cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination

A Punjani, JL Rubinstein, DJ Fleet, MA Brubaker - Nature methods, 2017 - nature.com
Single-particle electron cryomicroscopy (cryo-EM) is a powerful method for determining the
structures of biological macromolecules. With automated microscopes, cryo-EM data can …

AI is a viable alternative to high throughput screening: a 318-target study

Scientific reports, 2024 - nature.com
High throughput screening (HTS) is routinely used to identify bioactive small molecules. This
requires physical compounds, which limits coverage of accessible chemical space …

[HTML][HTML] Breaking cryo-EM resolution barriers to facilitate drug discovery

A Merk, A Bartesaghi, S Banerjee, V Falconieri, P Rao… - Cell, 2016 - cell.com
Recent advances in single-particle cryoelecton microscopy (cryo-EM) are enabling
generation of numerous near-atomic resolution structures for well-ordered protein …

Substrate processing by the Cdc48 ATPase complex is initiated by ubiquitin unfolding

EC Twomey, Z Ji, TE Wales, NO Bodnar, SB Ficarro… - Science, 2019 - science.org
INTRODUCTION Many cellular proteins are polyubiquitinated but cannot be directly
degraded by the proteasome because they are well folded, associated with binding …

Unravelling biological macromolecules with cryo-electron microscopy

R Fernandez-Leiro, SHW Scheres - Nature, 2016 - nature.com
Abstract Knowledge of the three-dimensional structures of proteins and other biological
macromolecules often aids understanding of how they perform complicated tasks in the cell …

Mechanistic insights into ER-associated protein degradation

X Wu, TA Rapoport - Current opinion in cell biology, 2018 - Elsevier
Misfolded proteins of the endoplasmic reticulum (ER) are discarded by a conserved process,
called ER-associated protein degradation (ERAD). ERAD substrates are retro-translocated …

VCP/p97-mediated unfolding as a principle in protein homeostasis and signaling

J van den Boom, H Meyer - Molecular cell, 2018 - cell.com
The AAA+-type ATPase p97 governs an ever-expanding number of cellular processes
reaching from degradation of damaged proteins and organelles to key signaling events and …

Molecular mechanism of substrate processing by the Cdc48 ATPase complex

NO Bodnar, TA Rapoport - Cell, 2017 - cell.com
Summary The Cdc48 ATPase and its cofactors Ufd1/Npl4 (UN) extract polyubiquitinated
proteins from membranes or macromolecular complexes, but how they perform these …