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Machine-learning models that learn from data to predict how protein sequence encodes function are emerging as a useful protein engineering tool. However, when using these models to suggest new protein designs, one must deal with the vast combinatorial complexity of protein sequences. Here, we review how to use a sequence-to-function machine-learning surrogate model to select sequences for experimental measurement. First, we discuss how to select sequences through a single round of machine-learning optimization. Then, we discuss sequential optimization, where the goal is to discover optimized sequences and improve the model across multiple rounds of training, optimization, and experimental measurement.
Boltzmann machines are energy-based models that have been shown to provide an accurate statistical description of domains of evolutionary-related protein and RNA families. They are parametrized in terms of local biases accounting for residue conserva
We used machine learning methods to predict NaV1.7 inhibitors and found the model RF-CDK that performed best on the imbalanced dataset. Using the RF-CDK model for screening drugs, we got effective compounds K1. We use the cell patch clamp method to v
The biological function of a protein stems from its 3-dimensional structure, which is thermodynamically determined by the energetics of interatomic forces between its amino acid building blocks (the order of amino acids, known as the sequence, define
We develop a theoretical approach to the protein folding problem based on out-of-equilibrium stochastic dynamics. Within this framework, the computational difficulties related to the existence of large time scale gaps in the protein folding problem a
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, time-consuming