Electrostatics as a Guiding Principle in Understanding and Designing Enzymes

Enzyme design faces challenges related to the implementation of the basic principles that govern the catalytic activity in natural enzymes. In this work, we revisit basic electrostatic concepts that have been shown to explain the origin of enzymatic efficiency like preorganization and reorganization...

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Bibliographic Details
Published inJournal of chemical theory and computation Vol. 20; no. 5; pp. 1783 - 1795
Main Authors Ruiz-Pernía, J. Javier, Świderek, Katarzyna, Bertran, Joan, Moliner, Vicent, Tuñón, Iñaki
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 12.03.2024
Subjects
Catalytic activity
Catalytic Domain
Electric fields
Electrostatics
Enzymes
Machine learning
Principles
Proteins
Static Electricity
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Summary:Enzyme design faces challenges related to the implementation of the basic principles that govern the catalytic activity in natural enzymes. In this work, we revisit basic electrostatic concepts that have been shown to explain the origin of enzymatic efficiency like preorganization and reorganization. Using magnitudes such as the electrostatic potential and the electric field generated by the protein, we explain how these concepts work in different enzymes and how they can be used to rationalize the consequences of point mutations. We also discuss examples of protein design in which electrostatic effects have been implemented. For the near future, molecular simulations, coupled with the use of machine learning methods, can be used to implement electrostatics as a guiding principle for enzyme designs.
Bibliography:ObjectType-Article-2
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ISSN:1549-9618
1549-9626
DOI:10.1021/acs.jctc.3c01395