Issue #2: Meeko: Molecule Parametrization and Software Interoperability for Docking and Beyond.

Signal of the Day

Meeko: Molecule Parametrization and Software Interoperability for Docking and Beyond.

Molecule parametrization is an essential requirement to guarantee the accuracy of docking calculations. Parametrization includes a proper perception of chemical properties such as bonds, formal charges and protonation states. This includes large biological macromolecules, such as proteins and nucleic acids, and small molecules, such as ligands and cofactors. The structures of proteins and nucleic acids are challenging due to omission of several atoms from the structural model, and from the lack of connectivity and bond order information in the PDB and mmCIF file formats. For small molecules, the very large chemical diversity poses challenges for both validating correctness and providing accurate parameters. These challenges affect various modeling approaches like molecular docking and molecular dynamics. Moreover, several specialized methods (particularly in molecular docking) leverage specific chemical properties to add custom potentials, pseudoatoms, or manipulate atomic connectivity. To address these challenges, we developed Meeko, a molecular parametrization Python package that leverages the widely used RDKit cheminformatics library for a chemically accurate description of the molecular representation. Small molecules are modeled as single RDKit molecules, and biological macromolecules as multiple RDKit molecules, one for each residue. Meeko is highly customizable and designed to be easily scriptable for high-throughput processing, replacing MGLTools for receptor and ligand preparation.

Why this matters: Expands the searchable sequence space for novel folds and high-affinity binders.

Research & AI Updates

• AlphaFold and the architecture that cracked protein structure - Interesting Engineering — AlphaFold and the architecture that cracked protein structure    Interesting Engineering.
• AI pinpoints new drug target for treating monkeypox virus - BioTechniques — AI pinpoints new drug target for treating monkeypox virus    BioTechniques.
• Key Insights: Computational Structural Biology Workshop - Mirage News — Key Insights: Computational Structural Biology Workshop    Mirage News.

From the Industry

• Galux, Boehringer Ingelheim to Jointly Explore AI in Precision Protein Design - Contract Pharma — Galux, Boehringer Ingelheim to Jointly Explore AI in Precision Protein Design    Contract Pharma.
• Profluent Bio Partners with Ensoma for AI-Designed Base Editors in Stem Cell Therapies - SynBioBeta — Profluent Bio Partners with Ensoma for AI-Designed Base Editors in Stem Cell Therapies    SynBioBeta.
• Lindus Health, Quotient Sciences Partner to Accelerate Drug Development to Clinical Trials - Contract Pharma — Lindus Health, Quotient Sciences Partner to Accelerate Drug Development to Clinical Trials    Contract Pharma.

Quick Reads

From sweetener to risk factor: Network toxicology, molecular docking and molecular dynamics reveal the mechanism of aspartame in promoting coronary heart disease.

Aspartame, a widely used non-nutritive sweetener, has been epidemiologically linked to coronary heart disease (CHD), although the underlying mechanisms remain unclear. Read more →

Enzyme Engineering Database (EnzEngDB): a platform for sharing and interpreting sequence-function relationships across protein engineering campaigns.

The discovery and engineering of new enzymes is important across the bioeconomy, with diverse applications from foods to pharmaceuticals, sensors to agriculture. Read more →

Multi-target exploration of newly synthesized pyrazoline-quinoline derivatives via in vitro screening, QSAR, molecular docking, MD simulations, and DFT analysis.

The development of multifunctional therapeutic agents remains a promising strategy in modern drug discovery, particularly for diseases associated with oxidative stress, bacterial infections, and cancer progression. Read more →

Pipeline Tip

Index your BigWig files before visualization to save memory.

Resources & Tools

• Dataset: Uniprot Knowledgebase - The world’s most comprehensive resource for protein sequence and annotation.
• Tool: ReFOLD4 - Sophisticated protein structure refinement tool for improving model quality. View all tools →
• Event: Protein Design Hub (LinkedIn Group) (Ongoing)
• Job: Mercor hiring Senior Bioinformatics Scientist in Greater Montreal Metropolitan Area - LinkedIn at Bioinformatics Careers

The protein structure is the language of life; design is its poetry. — Recep Adiyaman