Knowledge-based De novo Protein Design Service

Knowledge-based de novo protein design explores the full sequence space, guided by the physical principles that underlie protein folding. The computational methodology has advanced to the point that a wide range of structures can be designed from scratch with atomic-level accuracy. Creative Biolabs is dedicated to establishing the most exquisite service platform for our clients and our one-stop protein engineering services can provide comprehensive technical support to advance our clients' projects.

Introduction to De novo Protein Design

De novo protein design generally begins with a large set of alternative conformations. Design positions are then chosen to be mutated. Ab initio structure-prediction calculations are carried out to determine whether the designed structure is the lowest-energy state of the designed sequence. Achieving this goal has required the investigation of sequence-independent constraints on backbone geometry. One constraint comes from the connectivity of the polypeptide chain and the requirement that the polar atoms of the backbone come into contact with the solvent in exposed loops. Another constraint comes from the limited flexibility of the polypeptide chain, which restricts the lengths of the loops that connect α-helices and β-sheets in various packing orientations. The algorithms for sampling come from the same classes of techniques used in protein folding. Designed sequences may then be clustered and evaluated with a more detailed scoring function. The design produces one or many sequences that are predicted to fold into the input structure, often with enhanced biophysical characteristics.

Fig.1 Schematic representation of knowledge-based de novo protein design.

Services

In de novo protein design, the ultimate objective is to identify amino acid sequences that fold into proteins with desired functions. De novo protein design can be looked upon as a product design problem on the molecular scale. We can provide the following three de novo protein design services to meet customers' specific requirements.

αβ folds design

The design approach mainly consists of three steps. First, an overall topology ‘blueprint' that is consistent with the backbone design principles is created. Second, protein backbones that are compatible with the blueprint are assembled from protein structure fragments using a Monte Carlo approach. Last, sequence-structure pairs with very low energy are achieved through a series of optimization methods.

Repeat proteins design

The effort to construct de novo proteins with ideal backbone arrangements has led to the design of proteins with internal symmetry in which a single idealized unit is repeated numerous times. Internal symmetry reduces the size of the sequence space that must be searched and enables a relatively small unit with a known sequence-structure combination to be reused repeatedly to build larger proteins.

Parametric helical bundles

The parametric equations can generate the idealized bundles of α-helices in parallel or antiparallel orientations in which the helices have arbitrary lengths, phasing, relative orientations, and twists. The helical bundles can be used directly in sequence-design calculations, yielding multiple-subunit oligomeric structures, or the helices can first be connected with loops to yield a single chain.

Creative Biolabs has been involved in the field of protein engineering for many years and we are fully committed to working with you to facilitate the successful completion of the projects. We have accumulated a wealth of experience from the accomplished projects and are very proud of our high-quality platforms to meet diverse needs from our clients. If you are interested in our services, please contact us for more details.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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