De Novo Protein Design

De novo protein design, also known as "the inverse protein folding problem", is a computational approach to protein design from scratch, rather than using a known protein structure. Identification of a primary sequence that can fold properly in to the desired structural topology forms the basis for the de novo design. In general, the design is realized in three steps; i) building a protein backbone, ii) sequence optimization and (iii) computational and experimental validation of selected sequence-structure match.

To design a protein from scratch, backbone building is the first and essential step, where secondary elements like α-helices, β-strands and loops are assembled with the assistance of machine learning with specified computational algorithms. Next, appropriate sequence is generated and optimized for desired conformation. To achieve this, many methods have been developed using either molecular mechanic energy functions, or knowledge based potential, or a hybrid of both functions. Finally, after checking the folding criteria of the target protein, the selected sequences will be evaluated computationally and further confirmed experimentally.

Creative BioMart provides services of de novo protein design based on customer's requirement. With advanced computational and experimental approaches, we offer professional one-stop services:

• Backbone building.
• Sequence design and optimization.
• Structure based prediction.
• Target protein expression and purification.
• X-ray crystallography or NMR spectroscopy validation.

Reference:

1. Gulati, K., Poluri, K.M. (2016) An overview of computational and experimental methods for designing novel proteins. Recent Patents on Biotechnology. 10: 235-263.

Figure 1 The strategy adapted for de novo designing of proteins.
(Recent Patents on Biotechnology 2016)