Computational Approaches for Rational Design of Proteins With Novel Functionalities

Abstract

Proteins are the most multifaceted macromolecules in living systems and have various important functions, including structural, catalytic, sensory, and regulatory functions. Rational design of enzymes is a great challenge to our understanding of protein structure and physical chemistry and has numerous potential applications. Protein design algorithms have been applied to design or engineer proteins that fold, fold faster, catalyze, catalyze faster, signal, and adopt preferred conformational states. The field of de novo protein design, although only a few decades old, is beginning to produce exciting results. Developments in this field are already having a significant impact on biotechnology and chemical biology. The application of powerful computational methods for functional protein designing has recently succeeded at engineering target activities. Here, we review recently reported de novo functional proteins that were developed using various protein design approaches, including rational design, computational optimization, and selection from combinatorial libraries, highlighting recent advances and successes.

Maximizing Stability in Industrial Enzymes: Rational Design Approach – A Review

“…The introduction of Protein engineering in the early 1980s evolved from the knowledge of gene cloning, DNA sequencing and in-vitro DNA manipulations (cited in [4]). Majority of enzymes isolated from their natural source do not have the desired features for industrial application in one way or the other.…”

“…The increasing usage of enzymes in industrial processes and household catalysis has spurred the development of protein engineering methodologies to produce novel enzymes with new or improved properties. The advances in recombinant DNA technology, high throughput in technology, genomics and proteomics have fueled the development of novel enzymes and biocatalytic processes (cited in [4]).…”

“…The creation of biocatalysts from scratch enables scientists and engineers to build synthetic enzyme for a series of different chemical reactions (cited in [4]). Rational design is a strategy in protein engineering where proteins with improved characteristics are created based on the available information obtained from the three-dimensional structure and the relationship between protein structure and its function, which scientists believe over the years play a crucial role in protein`s function.…”

“…The enzyme biocatalysts required for industrial processes need to withstand conditions that they are not usually exposed to within their natural environments (cited in [1]). However, enzymes found in nature have been exploited in industries due to their inherent catalytic properties in complex chemical processes, under mild experimental and environmental conditions [4].…”

Properties and Applications of Extremozymes from Deep-Sea Extremophilic Microorganisms: A Mini Review

“…One method that can be used to stabilise proteins is protein engineering [29,30], which has become a powerful approach for altering or improving enzymatic characteristics in the past two decades. Protein engineering is divided into the following two methods: (1) directed evolution, where a random mutagenesis is applied to a protein [31]; and (2) rational protein design, where knowledge of the structure and function of the protein is exploited to modify its characteristics [32]. Both these methods have been successfully applied to increase the activity, selectivity and thermostability of proteins.…”