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Predicting the impact of single-point amino acid mutations on protein stability is essential for understanding disease mechanisms and advancing drug development. Protein stability, quantified by changes in Gibbs free energy ($\Delta\Delta…

Machine Learning · Computer Science 2025-01-31 Karishma Thakrar , Jiangqin Ma , Max Diamond , Akash Patel

A basic question of protein structural studies is to which extent mutations affect the stability. This question may be addressed starting from sequence and/or from structure. In proteomics and genomics studies prediction of protein…

Biomolecules · Quantitative Biology 2007-06-13 Emidio Capriotti , Piero Fariselli , Ivan Rossi , Rita Casadio

Stability is a key ingredient of protein fitness and its modification through targeted mutations has applications in various fields such as protein engineering, drug design and deleterious variant interpretation. Many studies have been…

Molecular Networks · Quantitative Biology 2021-11-09 Fabrizio Pucci , Martin Schwersensky , Marianne Rooman

We examine the stability of loss-minimizing training processes that are used for deep neural networks (DNN) and other classifiers. While a classifier is optimized during training through a so-called loss function, the performance of…

Analysis of PDEs · Mathematics 2020-10-05 Leonid Berlyand , Pierre-Emmanuel Jabin , C. Alex Safsten

Stabilizing proteins is a foundational step in protein engineering. However, the evolutionary pressure of all extant proteins makes identifying the scarce number of mutations that will improve thermodynamic stability challenging. Deep…

Biomolecules · Quantitative Biology 2023-11-01 Jeffrey Ouyang-Zhang , Daniel J. Diaz , Adam R. Klivans , Philipp Krähenbühl

In this work we evaluate the impact of digitally altered images on the performance of artificial neural networks. We explore factors that negatively affect the ability of an image classification model to produce consistent and accurate…

Computer Vision and Pattern Recognition · Computer Science 2020-08-14 Jason Stock , Andy Dolan , Tom Cavey

In this paper, we study the "stability" of machine learning (ML) models within the context of larger, complex NLP systems with continuous training data updates. For this study, we propose a methodology for the assessment of model stability…

Computation and Language · Computer Science 2022-01-19 Huiting Liu , Avinesh P. V. S. , Siddharth Patwardhan , Peter Grasch , Sachin Agarwal

The solution of linear inverse problems arising, for example, in signal and image processing is a challenging problem since the ill-conditioning amplifies, in the solution, the noise present in the data. Recently introduced algorithms based…

Numerical Analysis · Mathematics 2024-02-08 Davide Evangelista , James Nagy , Elena Morotti , Elena Loli Piccolomini

The accurate prediction of changes in protein stability under multiple amino acid substitutions is essential for realising true in-silico protein re-design. To this purpose, we propose improvements to state-of-the-art Deep learning (DL)…

Biomolecules · Quantitative Biology 2023-06-01 Sebastien Boyer , Sam Money-Kyrle , Oliver Bent

The generation of protein crystals is necessary for the study of protein molecular function and structure. This is done empirically by processing large numbers of crystallization trials and inspecting them regularly in search of those with…

Computer Vision and Pattern Recognition · Computer Science 2018-05-15 Soheil Ghafurian , Peter Orth , Corey Strickland , Hua Su , Sangita Patel , Steven Soisson , Belma Dogdas

The stability of model proteins with designed sequences is assessed in terms of the number of sequences (obtained from the designed sequence through mutations), which fold into 5the ``native'' conformation. By a complete enumeration of the…

Soft Condensed Matter · Physics 2009-10-31 R. A Broglia , G. Tiana , H. E. Roman , E. Vigezzi , E. I. Shakhnovich

Deep Neural Networks (DNNs) are becoming integral components of real world services relied upon by millions of users. Unfortunately, architects of these systems can find it difficult to ensure reliable performance as irrelevant details like…

Machine Learning · Computer Science 2023-05-22 Arghya Datta , Subhrangshu Nandi , Jingcheng Xu , Greg Ver Steeg , He Xie , Anoop Kumar , Aram Galstyan

Despite apparent human-level performances of deep neural networks (DNN), they behave fundamentally differently from humans. They easily change predictions when small corruptions such as blur and noise are applied on the input (lack of…

Computer Vision and Pattern Recognition · Computer Science 2020-03-10 Sanghyuk Chun , Seong Joon Oh , Sangdoo Yun , Dongyoon Han , Junsuk Choe , Youngjoon Yoo

We present a sequence-based probabilistic formalism that directly addresses co-operative effects in networks of interacting positions in proteins, providing significantly improved contact prediction, as well as accurate quantitative…

Quantitative Methods · Quantitative Biology 2012-07-12 Alan Lapedes , Bertrand Giraud , Christopher Jarzynski

In this paper we address the issue of output instability of deep neural networks: small perturbations in the visual input can significantly distort the feature embeddings and output of a neural network. Such instability affects many deep…

Computer Vision and Pattern Recognition · Computer Science 2016-04-18 Stephan Zheng , Yang Song , Thomas Leung , Ian Goodfellow

Here we study how mutations which change physical properties of cell proteins (stability) impact population survival and growth. In our model the genotype is presented as a set of N numbers, folding free energies of cells N proteins.…

Biomolecules · Quantitative Biology 2009-03-10 Peiqiu Chen , Eugene I. Shakhnovich

Protein mutations can significantly influence protein solubility, which results in altered protein functions and leads to various diseases. Despite of tremendous effort, machine learning prediction of protein solubility changes upon…

Biomolecules · Quantitative Biology 2023-11-06 JunJie Wee , Jiahui Chen , Kelin Xia , Guo-Wei Wei

Recent studies have shown that modern deep neural network classifiers are easy to fool, assuming that an adversary is able to slightly modify their inputs. Many papers have proposed adversarial attacks, defenses and methods to measure…

Machine Learning · Computer Science 2020-03-17 Igor Buzhinsky , Arseny Nerinovsky , Stavros Tripakis

Training a deep neural network (DNN) often involves stochastic optimization, which means each run will produce a different model. Several works suggest this variability is negligible when models have the same performance, which in the case…

Machine Learning · Statistics 2023-10-03 Sinjini Banerjee , Reilly Cannon , Tim Marrinan , Tony Chiang , Anand D. Sarwate

Structure determination is key to understanding protein function at a molecular level. Whilst significant advances have been made in predicting structure and function from amino acid sequence, researchers must still rely on expensive,…

Computer Vision and Pattern Recognition · Computer Science 2020-09-01 Alexander Hudson , Shaogang Gong
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