Directed evolution: methodologies and applications

Y Wang, P Xue, M Cao, T Yu, ST Lane… - Chemical reviews, 2021 - ACS Publications
Directed evolution aims to expedite the natural evolution process of biological molecules
and systems in a test tube through iterative rounds of gene diversifications and library …

Deep generative molecular design reshapes drug discovery

X Zeng, F Wang, Y Luo, S Kang, J Tang… - Cell Reports …, 2022 - cell.com
Recent advances and accomplishments of artificial intelligence (AI) and deep generative
models have established their usefulness in medicinal applications, especially in drug …

Illuminating protein space with a programmable generative model

JB Ingraham, M Baranov, Z Costello, KW Barber… - Nature, 2023 - nature.com
Three billion years of evolution has produced a tremendous diversity of protein molecules,
but the full potential of proteins is likely to be much greater. Accessing this potential has …

Disease variant prediction with deep generative models of evolutionary data

J Frazer, P Notin, M Dias, A Gomez, JK Min, K Brock… - Nature, 2021 - nature.com
Quantifying the pathogenicity of protein variants in human disease-related genes would
have a marked effect on clinical decisions, yet the overwhelming majority (over 98%) of …

Efficient evolution of human antibodies from general protein language models

BL Hie, VR Shanker, D Xu, TUJ Bruun… - Nature …, 2024 - nature.com
Natural evolution must explore a vast landscape of possible sequences for desirable yet
rare mutations, suggesting that learning from natural evolutionary strategies could guide …

Progen2: exploring the boundaries of protein language models

E Nijkamp, JA Ruffolo, EN Weinstein, N Naik, A Madani - Cell systems, 2023 - cell.com
Attention-based models trained on protein sequences have demonstrated incredible
success at classification and generation tasks relevant for artificial-intelligence-driven …

Language models enable zero-shot prediction of the effects of mutations on protein function

J Meier, R Rao, R Verkuil, J Liu… - Advances in neural …, 2021 - proceedings.neurips.cc
Modeling the effect of sequence variation on function is a fundamental problem for
understanding and designing proteins. Since evolution encodes information about function …

Mega-scale experimental analysis of protein folding stability in biology and design

K Tsuboyama, J Dauparas, J Chen, E Laine… - Nature, 2023 - nature.com
Advances in DNA sequencing and machine learning are providing insights into protein
sequences and structures on an enormous scale. However, the energetics driving folding …

Loss-of-function, gain-of-function and dominant-negative mutations have profoundly different effects on protein structure

L Gerasimavicius, BJ Livesey, JA Marsh - Nature communications, 2022 - nature.com
Most known pathogenic mutations occur in protein-coding regions of DNA and change the
way proteins are made. Taking protein structure into account has therefore provided great …

Protein remote homology detection and structural alignment using deep learning

T Hamamsy, JT Morton, R Blackwell, D Berenberg… - Nature …, 2024 - nature.com
Exploiting sequence–structure–function relationships in biotechnology requires improved
methods for aligning proteins that have low sequence similarity to previously annotated …