Fast Free Energies Predictions

OE Affinity Scoring calculates the ensemble average Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) energy and protein-ligand interaction score (knowledge-based scoring). The MMPBSA value represents a Boltzmann-weighted average over all major clusters. The knowledge-based scoring is an ensemble average representation of how stable the overall protein-ligand binding interactions are compared to the starting pose.

OE Affinity Scoring approach of combining physics-based and knowledge-based information quickly evaluates and triages ligands to prioritize the best candidates for further analysis, allowing you an efficient and cost-effective decision-making in the discovery process.

Yes, you can optimize your computational resources with OE Affinity Scoring. This combined physics-based and knowledge-based scoring method offers a faster and cost-effective approach to evaluate and triage ligands prior to full OE Affinity Relative Binding calculations. The system setup and short-trajectory MD equilibration performed for OE Affinity Scoring can be utilized for OE Affinity Relative Binding calculations, saving you valuable compute time.

OpenEye provides mapper tool for free energies calculations. The OE Affinity Mapper optimizes the Non-Equilibrium Switching (NES) process by selecting an efficient set of "edges" - transformations from one ligand to another. By mapping out these transformations, the NES process can estimate binding free energies efficiently for the entire ligand set. The selection of these "edges" is performed using a combination of Maximum Common Substructure (MCS) similarities and OpenEye's ROCS (shape and color) Score for a more accurate result.

Users have access to several edge mapper options for connecting ligands in binding free energies calculations, including OELOMAP, Single-hub Star Map, and Binary Star Map. With version 2022.2, users have the option to use automated Star Mapper.

Yes. Alchemical changes between ligands of different formal charges is now supported (with the December 2022 release). In addition, edge scores are also calculated for user provided mapper files.

OE Affinity offers versatile workflows (Floes) for a personalized experience, with options for both novice and expert users. Choose from pre-configured automated Floes or individual Floes for customized tasks with expert control.

Users get a comprehensive and interactive report of binding energy calculations. In addition, users can also seamlessly compare experimental affinity with the computed End-Point-Analysis results (predicted relative binding free energies).

OE Affinity Relative Binding offers fast and affordable free energy calculations with its Non-Equilibrium Switching approach. Test cases demonstrate the ability to run dozens of ligands in just a few hours for a low cost of a few hundred dollars.

OE Affinity Relative Binding, a highly efficient and cost-effective free energy calculation method, is adapted from the NES approach developed by Vytautas Gapsys in the Bert L. DeGroot Lab at the Max Planck Institute for Biophysical Chemistry.(Gapsys et al., Chem. Sci. 2020, 11, 1140-1152).

With the integration of proprietary OpenEye methods for system pre-equilibration and chimeric-molecule calculation, it delivers quick transitions through intermediate states and parallel sampling of short trajectories. This results in faster, yet equally accurate calculations compared to conventional equilibrium-based methods.

The OE Affinity Relative Binding method has been rigorously tested and validated on multiple datasets, including CDK2, PTP1B, Jnk1, p38, Thrombin, MCL1, Bace, and Tyk2. Open Force Field (OpenFF) and GAFF small molecule force field are available.

Kandall’s tau correlations show OpenEye’s method has comparable accuracy, using GAPSYS (2020) and FEP (JACS 15) datasets from literature. Results from these tests demonstrate that OpenEye's method has no significant differences in aggregate performance and is a reliable solution for free energy calculations.

Yes, with version 2023.2 and later, the use of the bespoke force field option is now available in Molecular Dynamics and Non-Equilibrium Switching.

OE Affinity provides users with a Maximum Likelihood Estimator method to predict the absolute binding affinities starting from the relative binding affinities and a set of reference experimental binding free energies. This estimated value will be provided only if the graph edges are well connected and some experimental binding free energies are provided.