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Protein variant libraries produced by site-directed mutagenesis are a useful tool utilized by protein engineers to explore variants with potentially improved properties, such as activity and stability. These libraries are commonly built by…

Data Structures and Algorithms · Computer Science 2022-11-28 Dimitris Papamichail , Madeline Febinger , Shm Almeda , Georgios Papamichail

Randomized libraries are increasingly popular in protein engineering and other biomedical research fields. Statistics of the libraries are useful to guide and evaluate randomized library construction. Previous works only give the mean of…

Quantitative Methods · Quantitative Biology 2024-05-28 Yong Kong

Variation and selection are the core principles of Darwinian evolution, yet quantitatively relating the diversity of a population to its capacity to respond to selection is challenging. Here, we examine this problem at a molecular level in…

Populations and Evolution · Quantitative Biology 2016-04-27 Sébastien Boyer , Dipanwita Biswas , Ananda Kumar Soshee , Natale Scaramozzino , Clément Nizak , Olivier Rivoire

BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar…

Populations and Evolution · Quantitative Biology 2009-04-16 Jesse D. Bloom , Zhongyi Lu , David Chen , Alpan Raval , Ophelia S. Venturelli , Frances H. Arnold

Whether evolution can be predicted is a key question in evolutionary biology. Here we set out to better understand the repeatability of evolution. We explored experimentally the effect of mutation supply and the strength of selective…

Populations and Evolution · Quantitative Biology 2017-09-13 Thomas van Dijk , Sungmin Hwang , Joachim Krug , J. Arjan G. M. de Visser , Mark P. Zwart

Biological machine learning is often bottlenecked by a lack of scaled data. One promising route to relieving data bottlenecks is through high throughput screens, which can experimentally test the activity of $10^6-10^{12}$ protein sequences…

Machine Learning · Statistics 2025-10-21 Eli N. Weinstein , Andrei Slabodkin , Mattia G. Gollub , Elizabeth B. Wood

A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the…

Populations and Evolution · Quantitative Biology 2019-08-27 Roman V. Belavkin , Alastair Channon , Elizabeth Aston , John Aston , Rok Krasovec , Christopher G. Knight

To reduce experimental effort associated with directed protein evolution and to explore the sequence space encoded by mutating multiple positions simultaneously, we incorporate machine learning in the directed evolution workflow.…

Biomolecules · Quantitative Biology 2020-01-07 Zachary Wu , S. B. Jennifer Kan , Russell D. Lewis , Bruce J. Wittmann , Frances H. Arnold

We propose a new, flexible approach for dynamically maintaining successful mutation rates in evolutionary algorithms using $k$-bit flip mutations. The algorithm adds successful mutation rates to an archive of promising rates that are…

Neural and Evolutionary Computing · Computer Science 2024-04-08 Martin S. Krejca , Carsten Witt

Enzyme is the major workhorse to carry out the diverse cellular functions. It catalyzes the biological reactions with a high specificity, with its topology playing a crucial role. For ecologically safe production of numerous bioproducts…

Biomolecules · Quantitative Biology 2021-06-04 Prabha Sankara Narayanan , Ashish Runthala

We investigate trends in the data-error scaling laws of machine learning (ML) models trained on discrete combinatorial spaces that are prone-to-mutation, such as proteins or organic small molecules. We trained and evaluated kernel ridge…

Chemical Physics · Physics 2025-10-10 Vanni Doffini , O. Anatole von Lilienfeld , Michael A. Nash

Protein mutations can have profound effects on biological function, making accurate prediction of property changes critical for drug discovery, protein engineering, and precision medicine. Current approaches rely on fine-tuning…

Machine Learning · Computer Science 2025-10-27 Srivathsan Badrinarayanan , Yue Su , Janghoon Ock , Alan Pham , Sanya Ahuja , Amir Barati Farimani

It is a long-standing question in origin-of-life research whether the information content of replicating molecules can be maintained in the presence of replication errors. Extending standard quasispecies models of non-enzymatic replication,…

Populations and Evolution · Quantitative Biology 2009-12-03 B. Obermayer , E. Frey

Designing protein mutants of both high stability and activity is a critical yet challenging task in protein engineering. Here, we introduce PRIME, a deep learning model, which can suggest protein mutants of improved stability and activity…

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

Polymerases select nucleotides before incorporating them for chemical synthesis during gene replication or transcription. How the selection proceeds stepwise efficiently to achieve sufficiently high fidelity and speed is essential for…

Biological Physics · Physics 2017-01-19 Jin Yu

Biologists use random transposon mutagenesis to construct knockout libraries for bacteria. Random mutagenesis offers cost and efficiency benefits over the standard site directed mutagenesis, but one can no longer ensure that all the…

Other Quantitative Biology · Quantitative Biology 2007-05-23 Oliver Will , Michael A Jacobs

The persistence of life requires populations to adapt at a rate commensurate with the dynamics of their environment. Successful populations that inhabit highly variable environments have evolved mechanisms to increase the likelihood of…

Genomics · Quantitative Biology 2007-05-23 Taison Tan , Leonard D. Bogarad , Michael W. Deem

Single domain proteins are thought to be tightly packed. The introduction of voids by mutations is often regarded as destabilizing. In this study we show that packing density for single domain proteins decreases with chain length. We find…

Soft Condensed Matter · Physics 2009-11-10 Jinfeng Zhang , Rong Chen , Chao Tang , Jie Liang

We investigate the mutation-selection dynamics for an evolutionary computation model based on Turing Machines that we introduced in a previous article. The use of Turing Machines allows for very simple mechanisms of code growth and code…

Populations and Evolution · Quantitative Biology 2015-03-17 Fabio Musso , Giovanni Feverati
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