J 2024

Protein representations: Encoding biological information for machine learning in biocatalysis

HARDING-LARSEN, David; Jonathan FUNK; Niklas Gesmar MADSEN; Hani GHARABLI; Carlos G. ACEVEDO-ROCHA et al.

Basic information

Original name

Protein representations: Encoding biological information for machine learning in biocatalysis

Authors

HARDING-LARSEN, David; Jonathan FUNK; Niklas Gesmar MADSEN; Hani GHARABLI; Carlos G. ACEVEDO-ROCHA; Stanislav MAZURENKO and Ditte Hededam WELNER

Edition

BIOTECHNOLOGY ADVANCES, OXFORD, PERGAMON-ELSEVIER SCIENCE LTD, 2024, 0734-9750

Other information

Language

English

Type of outcome

Article in a journal

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Marked to be transferred to RIV

Yes

RIV identification code

RIV/00216224:14310/24:00138463

Organization

Přírodovědecká fakulta – Repository – Repository

DOI

https://doi.org/10.1016/j.biotechadv.2024.108459

UT WoS

001332287000001

EID Scopus

2-s2.0-85205572232

Keywords in English

Machine learning; Biocatalysis; Protein representations; Enzyme engineering; Representation learning; Protein dynamics; Predictive models

Links

LM2023055, research and development project. 857560, interní kód Repo. RECETOX RI II, large research infrastructures.
Changed: 31/7/2025 00:50, RNDr. Daniel Jakubík

Abstract

In the original language

Enzymes offer a more environmentally friendly and low-impact solution to conventional chemistry, but they often require additional engineering for their application in industrial settings, an endeavour that is challenging and laborious. To address this issue, the power of machine learning can be harnessed to produce predictive models that enable the in silico study and engineering of improved enzymatic properties. Such machine learning models, however, require the conversion of the complex biological information to a numerical input, also called protein representations. These inputs demand special attention to ensure the training of accurate and precise models, and, in this review, we therefore examine the critical step of encoding protein information to numeric representations for use in machine learning. We selected the most important approaches for encoding the three distinct biological protein representations - primary sequence, 3D structure, and dynamics - to explore their requirements for employment and inductive biases. Combined representations of proteins and substrates are also introduced as emergent tools in biocatalysis. We propose the division of fixed representations, a collection of rule-based encoding strategies, and learned representations extracted from the latent spaces of large neural networks. To select the most suitable protein representation, we propose two main factors to consider. The first one is the model setup, which is influenced by the size of the training dataset and the choice of architecture. The second factor is the model objectives such as consideration about the assayed property, the difference between wild-type models and mutant predictors, and requirements for explainability. This review is aimed at serving as a source of information and guidance for properly representing enzymes in future machine learning models for biocatalysis.
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