Applications
RNA drugs 01
RNA drugs 02
Nostrum Biodiscovery specializes in designing and optimizing a wide range of nucleic acid modalities, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), messenger RNAs (mRNAs), aptamers, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), splicing stabilizers, among others. By tailoring these modalities to specific therapeutics and functional requirements, we enable cutting-edge solutions for gene regulation, protein expression, and precision-targeted therapies.
XNA-Hub is a pioneering platform devoted to the modeling and exploration of both natural and non-natural nucleic acids with pharmaceutical interest. It integrates advanced computational tools and innovative methodologies to accelerate the design and optimization of nucleic acid therapeutics.
3D Structure Prediction and Modeling: Accurate prediction and visualization of nucleic acid structures, including chemically modified sequences.
Automatic Parameterization of Chemical Modifications: Seamlessly incorporates non-natural nucleotides into computational workflows to evaluate novel therapeutic designs.
Plain and Biased MD Simulations to generate informative trajectories to characterize statistically-significant local and global observables.
Free Energy Calculations: Provides insights into the stability and dynamics of nucleic acids for enhanced predictive capabilities.
Applications:
Design of next-generation RNA and DNA therapeutics.
Exploration of novel chemical modifications.
Comprehensive analysis of RNA interactions within protein- or ligand-mediated complexes to uncover binding mechanisms, structural dynamics, and functional implications.
Nostrum Biodiscovery specializes in computational design and development of advanced vaccines, including areas such as mRNA stabilization, delivery optimization, lipid nanoparticle formulation, and conjugation technologies.
mRNA Stabilization: Strategies to enhance mRNA half-life and translational efficiency.
Delivery: Lipid nanoparticle (LNP) and other advanced delivery systems for targeted immune response.
Lipid Nanoparticle Formulation: Custom lipid compositions for optimal encapsulation.
Conjugation: Development of conjugated mRNA platforms for novel immunotherapeutic applications.
ParmBSC2, the state-of-the-art force field for natural and xeno nucleic acids, enables precise modeling of DNA and RNA, capturing their dynamics and accurately handling complex structures. Built on advanced quantum mechanics and machine learning, it realistically models stacking and non-bonded interactions. Extensively validated, Parmbsc2 consistently aligns with experimental data, maintaining nucleic acid structural integrity across diverse systems. Optimized for high-performance, it integrates smoothly with top molecular dynamics platforms, supporting scalable, large-scale simulations efficiently.
Specialized force field generation ensures accurate nucleic acid simulations:
Ad-hoc Parameterization: Custom parameter generation for unique nucleic acid chemistries.
Multilevel Parametrization: Bridging classical molecular mechanics and quantum-based methods.
Biophysics Validation: Rigorous validation through experimental and computational approaches.
Nostrum Biodiscovery leverages classical MD simulations, enhanced sampling methods and AI tools to design and optimize key properties of nucleic acid modalities. Our capabilities include precise thermodynamic profiling, folding prediction, and optimization of binding affinities. We specialize in elucidating RNA-protein, RNA-RNA, and DNA-RNA interactions to drive innovative therapeutic and diagnostic applications. Additionally, our expertise extends to reverse engineering nucleic acid structures and enhancing target recognition for specific and efficient molecular interactions.
Thermodynamics: Precise calculations of stability and free energy changes.
Folding: In-depth analysis of secondary and tertiary RNA/DNA structures.
Binding Affinity: Computational prediction and experimental validation of nucleic acid interactions.
RNA-Protein Interaction: Characterizing functional binding and co-regulation mechanisms.
RNA-RNA Interaction: Modeling complex regulatory networks.
DNA-RNA Interaction: Exploring hybridization and transcription dynamics.
Reverse Engineering: Deconvoluting sequence-function relationships for therapeutic applications.
Target Recognition: High-throughput prediction of nucleic acid-target binding specificity.
Our main focus areas include ASO, siRNA, and miRNA, whether in bonded or unbonded conditions. By leveraging classical MD simulations combined with enhanced sampling methods and AI, we analyze key events such as target recognition, binding interactions, and chemical engineering to optimize and personalize these processes.
