Mimicking hypomethylation of FUS requires liquid–liquid phase separation to induce synaptic dysfunctions

Autor: Seung Chan Kim, Scott J. Mitchell, Seema Qamar, Daniel J. Whitcomb, Marc-David Ruepp, Peter St George-Hyslop, Kwangwook Cho

Publikováno v: Acta Neuropathologica Communications, Vol 11, Iss 1, Pp 1-15 (2023)

Abstract The hypomethylation of fused in sarcoma (FUS) in frontotemporal lobar degeneration promotes the formation of irreversible condensates of FUS. However, the mechanisms by which these hypomethylated FUS condensates cause neuronal dysfunction ar

Externí odkaz: https://doaj.org/article/f1d094e7bd984d60b4f09d9494f5578d

Spatially non-uniform condensates emerge from dynamically arrested phase separation

Autor: Nadia A. Erkamp, Tomas Sneideris, Hannes Ausserwöger, Daoyuan Qian, Seema Qamar, Jonathon Nixon-Abell, Peter St George-Hyslop, Jeremy D. Schmit, David A. Weitz, Tuomas P. J. Knowles

Publikováno v: Nature Communications, Vol 14, Iss 1, Pp 1-8 (2023)

Biomolecular condensates with internal structure allow cells to further organise their processes. In this work the authors investigate how condensates can obtain an internal structure with droplets of dilute phase inside via kinetic, rather than pure

Externí odkaz: https://doaj.org/article/7c07f116ca21498c96519569ce628d42

BioNeMo Framework: a modular, high-performance library for AI model development in drug discovery

Autor: John, Peter St., Lin, Dejun, Binder, Polina, Greaves, Malcolm, Shah, Vega, John, John St., Lange, Adrian, Hsu, Patrick, Illango, Rajesh, Ramanathan, Arvind, Anandkumar, Anima, Brookes, David H, Busia, Akosua, Mahajan, Abhishaike, Malina, Stephen, Prasad, Neha, Sinai, Sam, Edwards, Lindsay, Gaudelet, Thomas, Regep, Cristian, Steinegger, Martin, Rost, Burkhard, Brace, Alexander, Hippe, Kyle, Naef, Luca, Kamata, Keisuke, Armstrong, George, Boyd, Kevin, Cao, Zhonglin, Chou, Han-Yi, Chu, Simon, Costa, Allan dos Santos, Darabi, Sajad, Dawson, Eric, Didi, Kieran, Fu, Cong, Geiger, Mario, Gill, Michelle, Hsu, Darren, Kaushik, Gagan, Korshunova, Maria, Kothen-Hill, Steven, Lee, Youhan, Liu, Meng, Livne, Micha, McClure, Zachary, Mitchell, Jonathan, Moradzadeh, Alireza, Mosafi, Ohad, Nashed, Youssef, Paliwal, Saee, Peng, Yuxing, Rabhi, Sara, Ramezanghorbani, Farhad, Reidenbach, Danny, Ricketts, Camir, Roland, Brian, Shah, Kushal, Shimko, Tyler, Sirelkhatim, Hassan, Srinivasan, Savitha, Stern, Abraham C, Toczydlowska, Dorota, Veccham, Srimukh Prasad, Venanzi, Niccolò Alberto Elia, Vorontsov, Anton, Wilber, Jared, Wilkinson, Isabel, Wong, Wei Jing, Xue, Eva, Ye, Cory, Yu, Xin, Zhang, Yang, Zhou, Guoqing, Zandstein, Becca, Dallago, Christian, Trentini, Bruno, Kucukbenli, Emine, Rvachov, Timur, Calleja, Eddie, Israeli, Johnny, Clifford, Harry, Haukioja, Risto, Haemel, Nicholas, Tretina, Kyle, Tadimeti, Neha, Costa, Anthony B

Artificial Intelligence models encoding biology and chemistry are opening new routes to high-throughput and high-quality in-silico drug development. However, their training increasingly relies on computational scale, with recent protein language mode

Externí odkaz: http://arxiv.org/abs/2411.10548

Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies

Autor: Tatiana Orme, Dena Hernandez, Owen A. Ross, Celia Kun-Rodrigues, Lee Darwent, Claire E. Shepherd, Laura Parkkinen, Olaf Ansorge, Lorraine Clark, Lawrence S. Honig, Karen Marder, Afina Lemstra, Ekaterina Rogaeva, Peter St. George-Hyslop, Elisabet Londos, Henrik Zetterberg, Kevin Morgan, Claire Troakes, Safa Al-Sarraj, Tammaryn Lashley, Janice Holton, Yaroslau Compta, Vivianna Van Deerlin, John Q. Trojanowski, Geidy E. Serrano, Thomas G. Beach, Suzanne Lesage, Douglas Galasko, Eliezer Masliah, Isabel Santana, Pau Pastor, Pentti J. Tienari, Liisa Myllykangas, Minna Oinas, Tamas Revesz, Andrew Lees, Brad F. Boeve, Ronald C. Petersen, Tanis J. Ferman, Valentina Escott-Price, Neill Graff-Radford, Nigel J. Cairns, John C. Morris, Stuart Pickering-Brown, David Mann, Glenda Halliday, David J. Stone, Dennis W. Dickson, John Hardy, Andrew Singleton, Rita Guerreiro, Jose Bras

Publikováno v: Acta Neuropathologica Communications, Vol 8, Iss 1, Pp 1-11 (2020)

Abstract Dementia with Lewy bodies (DLB) is a clinically heterogeneous disorder with a substantial burden on healthcare. Despite this, the genetic basis of the disorder is not well defined and its boundaries with other neurodegenerative diseases are

Externí odkaz: https://doaj.org/article/eb7da7eb422d4a428e7652ae48f842e3

Plug & play directed evolution of proteins with gradient-based discrete MCMC

Autor: Patrick Emami, Aidan Perreault, Jeffrey Law, David Biagioni, Peter St. John

Publikováno v: Machine Learning: Science and Technology, Vol 4, Iss 2, p 025014 (2023)

A long-standing goal of machine-learning-based protein engineering is to accelerate the discovery of novel mutations that improve the function of a known protein. We introduce a sampling framework for evolving proteins in silico that supports mixing

Externí odkaz: https://doaj.org/article/af758cbb072b477dbe6309a5650b0768