Why does conformational flexibility matter in drug design?
What are conformational ensembles? A conformational ensemble is a collection of the different 3D shapes a molecule can adopt in…
How much does 3D molecular modelling software cost?
Introduction 3D molecular modelling plays a vital role in modern drug discovery, offering powerful applications to streamline research, reduce costs,…
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…
Macrocyclic peptide optimisation: Integrating computational approaches with biophysical data
Introduction Using the integrated set of computational methods within the BioPharmics™ Platform, macrocycles can be effectively modelled for lead optimisation.…
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…
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.
Unmasking the true identity of rapamycin’s minor conformer
The solution structure of the minor conformer of rapamycin was investigated using a combination of NMR techniques and computational methods
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.
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.
ForceGen 3D structure and conformer generation: from small lead-like molecules to macrocyclic drugs
We introduce the ForceGen method for 3D structure generation and conformer elaboration of drug-like small molecules.
