Abstract

De novo protein design is a powerful methodology used to study natural functions in an artificial-protein context. Since its inception, it has been used to reproduce a plethora of reactions and uncover biophysical principles that are often difficult to extract from direct studies of natural proteins. Natural proteins are capable of assuming a variety of different structures and subsequently binding ligands at impressively high levels of both specificity and affinity. Here, we will review recent examples of de novo design studies on binding reactions for small molecules, nucleic acids, and the formation of protein-protein interactions. We will then discuss some new structural advances in the field. Finally, we will discuss some advancements in computational modeling and design approaches and provide an overview of some modern algorithmic tools being used to design these proteins.

Highlights

  • Design to Study Protein Structure, Binding is one of the most important and fundamental biological processes, underpinning everything from drug interactions to genetic regulation and cytoskeletal formation [1,2,3]

  • In this review we are primarily focusing on de novo protein design, which does not rely on naturally occurring proteins or mimicking sequences from nature, but rather starts from a totally abiological scaffold and introduces mutations based on the chemical principles needed for function and uses either knowledge-based or computational

  • More via in depth perbinding interactions starting with metal ions, that can be held For in place coordination spectives de novo protein design that both describe methodology and provide bonds, and on progressing to organic molecules, that must bethe held in place through non-polar more historyWe andwill context to the fieldwork we suggest following reviews and perspectives interactions

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Summary

Introduction

Design to Study Protein Structure, Binding is one of the most important and fundamental biological processes, underpinning everything from drug interactions to genetic regulation and cytoskeletal formation [1,2,3]. Protein design avoids many of these pitfalls by starting with a well-understood scaffold that has either a modest or no direct relation to natural sequences. There are different approaches to protein design, which vary mainly by how the mutations are introduced. These include directed evolution, redesign of natural proteins and de novo design. In this review we are primarily focusing on de novo protein design, which does not rely on naturally occurring proteins or mimicking sequences from nature, but rather starts from a totally abiological scaffold and introduces mutations based on the chemical principles needed for function and uses either knowledge-based or computational. 2 ofligand binding and organic chemical catalysis [10,11,12,13]

Process flow of of
Metal Binding Proteins and Related Functions
Porphyrin Cofactors
Hydrophobic Molecules
Transmembrane Proteins
Packing of the Hydrophobic Core and Structural Stability
Protein-Protein Interactions
Incorporation of protein logic with
Antimicrobial Peptides and Other Therapeutics
Using Protein Design to Combat COVID-19
Using De Novo Designed PPIs to Fight Cancer
Methods of Identifying PPIs
New Algorithms for Protein Design
Design from the Perspective of the Binding Pair
Findings
Conclusions
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