Electrostatics as a Guiding Principle in Understanding and Designing Enzymes
J. Javier Ruiz‐Pernía, Katarzyna Świderek, J. Bertrán, Vicent Moliner, Iñaki Tuñón
Abstract
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.