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Recently, several groups have used error-prone polymerase chain reactions to construct mutant libraries containing up to 27 nucleotide mutations per gene on average, and reported a striking observation: although retention of protein…

Quantitative Methods · Quantitative Biology 2007-05-23 D. Allan Drummond , Brent L. Iverson , George Georgiou , Frances H. Arnold

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

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

Fast numerical libraries have been a cornerstone of scientific computing for decades, but this comes at a price. Programs may be tied to vendor specific software ecosystems resulting in polluted, non-portable code. As we enter an era of…

Programming Languages · Computer Science 2019-10-10 Bruce Collie , Philip Ginsbach , Michael F. P. O'Boyle

Directed evolution is an iterative laboratory process of designing proteins with improved function by iteratively synthesizing new protein variants and evaluating their desired property with expensive and time-consuming biochemical…

Machine Learning · Computer Science 2025-09-08 Matouš Soldát , Jiří Kléma

How robust is the natural genetic code with respect to mistranslation errors? It has long been known that the genetic code is very efficient in limiting the effect of point mutation. A misread codon will commonly code either for the same…

Biological Physics · Physics 2009-11-03 Dimitri Gilis , Serge Massar , Nicolas Cerf , Marianne Rooman

DNA synthesis is considered as one of the most expensive components in current DNA storage systems. In this paper, focusing on a common synthesis machine, which generates multiple DNA strands in parallel following a fixed supersequence,we…

Information Theory · Computer Science 2025-05-13 Yajuan Liu , Tolga M. Duman

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

Sidechain rotamer libraries of the common amino acids of a protein are useful for folded protein structure determination and for generating ensembles of intrinsically disordered proteins (IDPs). However much of protein function is modulated…

Biological Physics · Physics 2024-05-07 Oufan Zhang , Shubhankar A. Naik , Zi Hao Liu , Julie Forman-Kay , Teresa Head-Gordon

Generating protein sequences conditioned on protein structures is an impactful technique for protein engineering. When synthesizing engineered proteins, they are commonly translated into DNA and expressed in an organism such as yeast. One…

Machine Learning · Computer Science 2024-09-27 Hannes Stark , Umesh Padia , Julia Balla , Cameron Diao , George Church

Synthetic microbiomes offer new possibilities for modulating microbiota, to address the barriers in multidtug resistance (MDR) research. We present a Bayesian optimization approach to enable efficient searching over the space of synthetic…

Quantitative Methods · Quantitative Biology 2024-05-02 Nisha Pillai , Bindu Nanduri , Michael J Rothrock , Zhiqian Chen , Mahalingam Ramkumar

Proteins are traditionally optimized through the costly construction and measurement of many mutants. Active Learning-assisted Directed Evolution (ALDE) alleviates that cost by predicting the best improvements and iteratively testing…

The design of large libraries of oligonucleotides having constant GC-content and satisfying Hamming distance constraints between oligonucleotides and their Watson-Crick complements is important in reducing hybridization errors in DNA…

Information Theory · Computer Science 2008-03-27 Yeow Meng Chee , San Ling

The genetic code underlying protein synthesis is a canonical example of a degenerate biological system. Degeneracies in physical and biological systems can be lifted by external perturbations thus allowing degenerate systems to exhibit a…

Genomics · Quantitative Biology 2013-04-23 Arvind R. Subramaniam , Tao Pan , Philippe Cluzel

This paper presents a novel Differential Evolution algorithm for protein folding optimization that is applied to a three-dimensional AB off-lattice model. The proposed algorithm includes two new mechanisms. A local search is used to improve…

Artificial Intelligence · Computer Science 2018-05-08 Borko Bošković , Janez Brest

Predicting the effect of mutations in proteins is one of the most critical challenges in protein engineering; by knowing the effect a substitution of one (or several) residues in the protein's sequence has on its overall properties, could…

Computational Engineering, Finance, and Science · Computer Science 2020-10-08 David Medina-Ortiz , Sebastian Contreras , Juan Amado-Hinojosa , Jorge Torres-Almonacid , Juan A. Asenjo , Marcelo Navarrete , Álvaro Olivera-Nappa

Structure-based virtual screening is an important tool in early stage drug discovery that scores the interactions between a target protein and candidate ligands. As virtual libraries continue to grow (in excess of $10^8$ molecules), so too…

Quantitative Methods · Quantitative Biology 2021-05-11 David E. Graff , Eugene I. Shakhnovich , Connor W. Coley

Ultra-large make-on-demand compound libraries now contain billions of readily available compounds. This represents a golden opportunity for in-silico drug discovery. One challenge, however, is the time and computational cost of an…

Quantitative Methods · Quantitative Biology 2025-12-10 Paul Eisenhuth , Fabian Liessmann , Rocco Moretti , Jens Meiler

Directed evolution is a versatile technique in protein engineering that mimics the process of natural selection by iteratively alternating between mutagenesis and screening in order to search for sequences that optimize a given property of…

Biomolecules · Quantitative Biology 2024-05-02 Lixue Cheng , Ziyi Yang , Changyu Hsieh , Benben Liao , Shengyu Zhang

Efficient protein synthesis depends on the availability of charged tRNA molecules. With 61 different codons, shifting the balance among the tRNA abundances can lead to large changes in the protein synthesis rate. Previous theoretical work…

Subcellular Processes · Quantitative Biology 2020-01-01 Rebecca J. Rousseau , William Bialek
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