Bulletin of the American Physical Society
APS March Meeting 2022
Volume 67, Number 3
Monday–Friday, March 14–18, 2022; Chicago
Session Z18: Biological and Charged Polymers
11:30 AM–2:18 PM,
Friday, March 18, 2022
Room: McCormick Place W-184D
Sponsoring
Unit:
DPOLY
Chair: Sibani Lisa Biswal, Rice University
Abstract: Z18.00004 : Single-sequence protein structure prediction using language models and deep learning*
12:06 PM–12:18 PM
Presenter:
Nazim Bouatta
(Harvard Medical School)
Author:
Nazim Bouatta
(Harvard Medical School)
AlphaFold2 and related computational systems predict protein structure using deep learning and co-evolutionary relationships encoded in multiple sequence alignments (MSAs). Despite the outstanding performance of AlphaFold2, predicting the structures of single sequences using deep learning nonetheless remains a challenge. The requirement in AlphaFold2 for co-evolutionary information from MSAs makes it less performative with proteins that lack sequence homologs, currently estimated at ~20% of all metagenomic protein sequences and ~11% of eukaryotic and viral proteins. On the other hand, protein design and studies quantifying the effects of sequence variation on function also require single-sequence structure prediction. I will describe the development of an end-to-end differentiable recurrent geometric network that uses a protein language model (AminoBERT) to learn latent structural information from unaligned proteins and a geometric module that compactly represents Cα backbone geometry in terms of Frenet-Serret formulas. Our model outperforms AlphaFold2 and RoseTTAFold on orphan proteins and classes of designed proteins while achieving a 106-fold reduction in compute time. These findings demonstrate the practical and theoretical strengths of protein language models in structure prediction.
*This work is supported by the DARPA PANACEA program grant HR0011-19-2-0022 and NCI grant U54-CA225088.
Follow Us |
Engage
Become an APS Member |
My APS
Renew Membership |
Information for |
About APSThe American Physical Society (APS) is a non-profit membership organization working to advance the knowledge of physics. |
© 2024 American Physical Society
| All rights reserved | Terms of Use
| Contact Us
Headquarters
1 Physics Ellipse, College Park, MD 20740-3844
(301) 209-3200
Editorial Office
100 Motor Pkwy, Suite 110, Hauppauge, NY 11788
(631) 591-4000
Office of Public Affairs
529 14th St NW, Suite 1050, Washington, D.C. 20045-2001
(202) 662-8700