Alpha Fold

Introduction

The eProtein Discovery™ Cloud platform integrates AlphaFold to provide a structure-guided approach to protein engineering. By combining in silico 3D modeling with automated screening, researchers can transition from a primary sequence to a purified, soluble protein in approximately 48 hours.

This integration enables users to identify structural impediments to expression and solubility before committing to wet-lab experiments.

Core Functionalities

AI-Driven Structural Prediction Upon entering a protein sequence, the software utilizes AlphaFold to generate high-confidence structural models.

Processing Time: Predictive data typically becomes available within minutes to hours, depending on sequence length and complexity.
Residue-Level Insights: Users can examine specific residues to understand local folding environments and potential post-translational modification sites.

Structural Analysis & Visualization The platform provides several dynamic visualization modes to assess the "manufacturability" of a protein construct:

Confidence Metrics (pLDDT): High-resolution mapping of AlphaFold’s per-residue confidence scores.
Hydrophobicity Mapping: Identification of exposed hydrophobic patches that may lead to aggregation or poor solubility.
PAE Plots: Predicted Aligned Error plots help determine the relative orientation of domains and the flexibility of linkers.
Domain Annotation: Automated identification of functional domains to guide truncation strategies.

Rational Construct Design (Variant Editor) The integrated Protein Variant Editor allows for high-precision engineering of novel constructs. Users can:

Truncate Regions: Remove disordered or "hard-to-express" N- or C-termini.
Domain Selection: Isolate specific domains of interest for targeted study.
Linker Integration: Insert custom linkers to stabilize multi-domain proteins or fusion tags.
Mutational Analysis: Design and validate point mutations to improve stability or function.

Technical Workflow

Sequence Input: Upload or paste the amino acid sequence into the Cloud interface.
AlphaFold Generation: Initiate the 3D modeling process to obtain structural predictions.
Bioinformatic Validation: Review Multiple Sequence Alignments (MSA) and confidence scores to verify the model's reliability.
Construct Refinement: Use the structural data to modify the sequence (e.g., removing hydrophobic loops or disordered regions).
Benchtop Execution: Export the optimized design for rapid automated screening and expression.

Nuclera Technical Support:
UK Phone +44 1223 942 761
US Phone: +1 508-306-1297
Email: techsupport@nuclera.com

Offices:
Nuclera UK (HQ):
One Vision Park, Station Road, Cambridge, CB24 9NP, UK

Nuclera USA:
1000 Technology Park Drive, Suite B, Billerica MA 01821, USA

www.nuclera.com

Introduction​

Core Functionalities​

Technical Workflow​

Introduction

Core Functionalities

Technical Workflow