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…
What are conformational ensembles? A conformational ensemble is a collection of the different 3D shapes a molecule can adopt in…
Introduction 3D molecular modelling plays a vital role in modern drug discovery, offering powerful applications to streamline research, reduce costs,…
The QuanSA method To define a ‘pocket field’, an initial alignment of all training molecules is constructed and function parameters…
Binding affinity prediction continues to be a challenge in computer-aided drug design, especially in the absence of a high-quality target…
Optibrium’s QuanSA 3D-QSAR method uses an active learning approach to successfully and more efficiently identify a mimic of a macrocyclic natural product
This article discusses logic fallacies in the context of off-target predictive modelling.
Computational approaches for binding affinity prediction are most frequently demonstrated through cross-validation within a series of molecules or through performance shown on a blinded test set. Here, we show how such a system performs in an iterative, temporal lead optimization exercise. A series of gyrase inhibitors with known synthetic order formed the set of molecules that could be selected for “synthesis.”
Surflex-QMOD integrates chemical structure and activity data to produce physically-realistic models for binding 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.
Scaffold replacement as part of an optimisation process that requires maintenance of potency, desirable biodistribution, metabolic stability, and considerations of synthesis at very large scale is a complex challenge.
We present results on the extent to which physics-based simulation (exemplified by FEP+) and focused machine learning (exemplified by QuanSA) are complementary for ligand affinity prediction.
We introduce the QuanSA method for inducing physically meaningful field-based models of ligand binding pockets based on structure-activity data alone.