Diverse molecular mechanisms underlying pathogenic protein mutations: beyond the loss-of-function paradigm

L Backwell, JA Marsh - Annual review of genomics and human …, 2022 - annualreviews.org
Most known disease-causing mutations occur in protein-coding regions of DNA. While some
of these involve a loss of protein function (eg, through premature stop codons or missense …

Folding and misfolding of human membrane proteins in health and disease: from single molecules to cellular proteostasis

JT Marinko, H Huang, WD Penn, JA Capra… - Chemical …, 2019 - ACS Publications
Advances over the past 25 years have revealed much about how the structural properties of
membranes and associated proteins are linked to the thermodynamics and kinetics of …

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 …

[HTML][HTML] Can predicted protein 3D structures provide reliable insights into whether missense variants are disease associated?

S Ittisoponpisan, SA Islam, T Khanna, E Alhuzimi… - Journal of molecular …, 2019 - Elsevier
Abstract Knowledge of protein structure can be used to predict the phenotypic consequence
of a missense variant. Since structural coverage of the human proteome can be roughly …

Mechanisms of SARS-CoV-2 evolution revealing vaccine-resistant mutations in Europe and America

R Wang, J Chen, GW Wei - The journal of physical chemistry …, 2021 - ACS Publications
The importance of understanding SARS-CoV-2 evolution cannot be overlooked. Recent
studies confirm that natural selection is the dominating mechanism of SARS-CoV-2 …

Multiplex assessment of protein variant abundance by massively parallel sequencing

KA Matreyek, LM Starita, JJ Stephany, B Martin… - Nature …, 2018 - nature.com
Determining the pathogenicity of genetic variants is a critical challenge, and functional
assessment is often the only option. Experimentally characterizing millions of possible …

Variant interpretation: functional assays to the rescue

LM Starita, N Ahituv, MJ Dunham, JO Kitzman… - The American Journal of …, 2017 - cell.com
Classical genetic approaches for interpreting variants, such as case-control or co-
segregation studies, require finding many individuals with each variant. Because the …

TopologyNet: Topology based deep convolutional and multi-task neural networks for biomolecular property predictions

Z Cang, GW Wei - PLoS computational biology, 2017 - journals.plos.org
Although deep learning approaches have had tremendous success in image, video and
audio processing, computer vision, and speech recognition, their applications to three …

Emerging vaccine-breakthrough SARS-CoV-2 variants

R Wang, J Chen, Y Hozumi, C Yin… - ACS infectious …, 2022 - ACS Publications
The surge of COVID-19 infections has been fueled by new SARS-CoV-2 variants, namely
Alpha, Beta, Gamma, Delta, and so forth. The molecular mechanism underlying such surge …