How can I model large molecules like macrocycles?
What comprises large molecules? When we talk about “large molecules,” we often think of biologics like monoclonal antibodies, proteins, and…
Optibrium demonstrates superior molecular docking method for small molecules and macrocycles
CAMBRIDGE, UK, 22 October 2024 – Optibrium, a leading developer of software and AI solutions for molecular design today announced…
Structure-based pose prediction: Non-cognate docking extended to macrocyclic ligands
In this paper, we describe an extended benchmark for non-cognate docking of macrocyclic ligands, and the superior performance of Surflex-Dock…
Molecular docking: Extrapolating to new scaffolds with Surflex-Dock
Interested in improving your binding mode predictions? Surflex-Dock is a unique method for molecular docking, offering automatic pipelines for ensemble docking, applicable to both small molecules and large peptidic macrocycles alike.
Complex peptide macrocycle optimisation: combining NMR restraints with conformational analysis to guide structure-based and ligand-based design
Systematic optimisation of large macrocyclic peptide ligands is a serious challenge. Here, we describe an approach for lead optimisation using the PD-1/PD-L1 system as a retrospective example of moving from initial lead compound to clinical candidate.
A distributional model of bound ligand conformational strain: from small molecules to large peptidic macrocycles
We show that the distribution of expected global strain energy values is dependent on molecular size in a superlinear manner. The distribution of strain energy follows a rectified normal distribution whose mean and variance are related to conformational complexity.
Conformational strain of macrocyclic peptides in ligand–receptor complexes based on advanced refinement of bound-state conformers
To better understand conformational propensities, global strain energies were estimated for 156 protein-macrocyclic peptide cocrystal structures.
XGen: real-space fitting of complex ligand conformational ensembles to x-ray electron density maps
We report a new method for X-ray density ligand fitting and refinement that is suitable for a wide variety of small-molecule ligands, including macrocycles.
Complex macrocycle exploration: parallel, heuristic, and constraint-based conformer generation using ForceGen
ForceGen is both faster and more accurate than the best of all tested methods on a very large, independently curated benchmark of 2859 PDB ligands. In this study, the primary results are on macrocycles, including results for 431 unique examples from four separate benchmarks.
Extrapolative prediction using physically-based QSAR
Surflex-QMOD integrates chemical structure and activity data to produce physically-realistic models for binding affinity prediction.
Knowledge-guided docking: accurate prospective prediction of bound configurations of novel ligands using Surflex-Dock
We present an approach that uses structural information known prior to a particular cutoff-date to make predictions on ligands whose bounds structures were determined later. The knowledge-guided docking protocol was tested on a set of ten protein targets using a total of 949 ligands.
Chemical and protein structural basis for biological crosstalk between PPARα and COX enzymes
Here we present an analysis of novel drug/target predictions, focusing on those that were not obvious based on known pharmacological crosstalk.
A structure-guided approach for protein pocket modeling and affinity prediction
We present a hybrid structure-guided strategy that combines molecular similarity, docking, and multiple-instance learning such that information from protein structures can be used to inform models of structure–activity relationships.
