Research & Innovation Analysis
ABACUS-T: Revolutionizing Protein Engineering with Multimodal Inverse Folding
ABACUS-T addresses a critical challenge in protein engineering: enhancing structural stability without compromising functional activity. By integrating detailed atomic sidechains, ligand interactions, pre-trained protein language models, multiple backbone conformational states, and evolutionary information, ABACUS-T achieves superior precision and functional preservation. This breakthrough allows for the simultaneous mutation of dozens of residues, leading to substantial improvements in thermostability and catalytic activity with minimal experimental screening.
Executive Impact: Key Achievements of ABACUS-T
ABACUS-T demonstrates significant advancements in protein engineering, delivering tangible results for complex biological challenges.
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Higher Affinity Achieved
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Thermostability Increase
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Residues Mutated Simultaneously
Deep Analysis & Enterprise Applications
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Inverse Folding Methodology
Traditional inverse folding often struggles with functional preservation. ABACUS-T introduces a novel multimodal approach that decodes both residue types and sidechain conformations at each denoising step. This self-conditioning, combined with large pre-trained language models like ESM, significantly improves the recovery rates of functionally important pocket and catalytic residues. It represents a significant leap forward in generating foldable and functionally active sequences.
Multimodal Integration
ABACUS-T unifies several crucial data types: detailed atomic sidechains, ligand interactions, multiple backbone conformational states, and evolutionary information from multiple sequence alignments (MSA). This comprehensive integration allows the model to capture complex spatial contexts, residue-residue interactions, and functional constraints, leading to more robust protein redesign than previous single-modality models.
Functional Enhancement
Beyond stability, ABACUS-T demonstrates its ability to preserve and even improve catalytic activity. Case studies show redesigned enzymes maintaining or surpassing wild-type activity, and an allose binding protein achieving 17-fold higher affinity. This capability to design sequences that balance stability with function, without explicit manual fixation of functional residues, marks a substantial advancement for biotechnological applications.
17X
Higher Affinity Achieved for Allose Binding
Enterprise Process Flow
Noised Sequence Input
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Predict Residue & Sidechain Types
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Re-mask Low Confidence Positions
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Iterative Denoising & Refinement
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Functional Protein Output
| Metric | ABACUS-T | ProteinMPNN | ESM-IF | LigandMPNN |
|---|---|---|---|---|
| Overall Sequence Recovery Rate | 0.63-0.65 | 0.55-0.56 | 0.59-0.59 | 0.53-0.54 |
| Pocket Residue Recovery Rate | 0.75-0.76 | 0.55-0.54 | 0.62-0.61 | 0.61-0.60 |
| KL Divergence (Residue Comp.) | 0.008 | 0.042 | 0.035 | 0.018 |
| Predicted PLDDT Scores (Higher is Better) | 83.8-85.4 | 82.1-84.5 | 82.0-83.5 | 83.9-85.7 |
| Predicted scRMSD (Lower is Better) | 2.79-1.70 | 3.03-1.76 | 2.96-1.93 | 2.72-1.70 |
Case Study: High Thermostability Xylanase
ABACUS-T was used to redesign endo-1,4-β-xylanase, an enzyme crucial for biomass degradation. While natural xylanase lost 86-99.9% activity after 10 min at 40-60°C, the ABACUS-T designed variant (pxyl3-0.5), with 63 mutations, maintained over 50% residual activity even after 50 min at 80°C. Its melting temperature (Tm) increased from 41°C to 60°C, and it exhibited full reversibility of thermal denaturation, restoring 100% activity. This demonstrates ABACUS-T’s capacity to engineer enzymes for extreme conditions without compromising catalytic function, achieving enhancements that would be unfeasible with traditional step-wise mutation approaches.
Case Study: Robust TEM β-Lactamase
TEM β-lactamase was redesigned with ABACUS-T to improve resistance to harsh conditions. The designed variant 'tlact2' exhibited a remarkable increase in melting temperature (Tm) from 49°C to 72°C. Critically, variants like 'plact2-0.5' showed over two times higher catalytic activity than the natural protein at room temperature, while 'plact2-0.2' retained ~75% activity after 60 min at 50°C. This highlights ABACUS-T's ability to navigate the trade-off between stability and catalytic activity, producing highly functional and stable enzymes through extensive, simultaneous mutations.
Case Study: Altered Substrate Specificity in OXA β-Lactamase
ABACUS-T was applied to OXA β-lactamase to rationally alter its substrate selectivity for three different β-lactam substrates: cefotaxime, ceftazidime, and imipenem. The designed enzymes successfully shifted selectivity, with variants showing significantly enhanced activity for their target substrates (e.g., ceftazidime variants showed 8-10 times higher activity than native). Simultaneously, these redesigned proteins achieved hyper-thermostability, with melting temperatures (Tm) exceeding 90°C, far surpassing the native enzyme's 52°C. This multifaceted engineering, achieving both altered function and extreme stability, demonstrates ABACUS-T's potential for developing enzymes with custom substrate profiles for specific biotechnological applications.
Calculate Your Potential ROI with ABACUS-T
Estimate the transformative impact of ABACUS-T on your protein engineering projects. Our advanced inverse folding capabilities can drastically reduce development costs and accelerate time-to-market.
Estimated Annual Savings
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Scientist Hours Reclaimed Annually
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Our Proven ABACUS-T Implementation Roadmap
A phased approach ensures seamless integration and maximum impact for your enterprise. From initial analysis to full-scale deployment, we guide you every step of the way.
Phase 1: Discovery & Design Consultation
Comprehensive analysis of your target protein, functional requirements, and stability goals using ABACUS-T's multimodal inputs (structure, ligand, MSA, conformational states). We define project scope and success metrics.
Phase 2: AI-Driven Sequence Generation
Leveraging ABACUS-T to generate diverse candidate protein sequences, simultaneously optimizing for stability, function, and desired properties. Iterative computational screening identifies top-performing variants.
Phase 3: Experimental Validation & Refinement
Rapid synthesis and experimental characterization of top candidates (e.g., thermostability, activity, affinity). ABACUS-T's minimal screening requirements accelerate this crucial step.
Phase 4: Optimization & Production Scaling
Further fine-tuning of lead candidates and guidance on scaling up production for industrial application, ensuring your engineered proteins deliver sustained value.
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