LEAD OPTIMIZATION

Fast Free Energies Predictions

Discover drugs with speed and ease using the OpenEye Affinity (OE Affinity) set of tools designed to accurately estimate binding free energies.

With a focus on cutting-edge science and technology, OE Affinity simplifies the process of drug discovery by delivering powerful tools directly to your web browser on Orion® cloud modeling platform. There's no software to install; all you need is a web browser. Simply log in and get started!

OpenEye’s Affinity tools let you calculate binding free energies, with accuracy and speed. Scientists can access the automated process conveniently from their web browsers.

Features

Proven. Adapted from published work from the DeGroot Lab at Max Planck Institute
Accurate. Validated on internal and external datasets
Flexible. Edge mapper options for connecting ligands ncluding OELOMAP, Single-hub Star Map, and Binary Star Map.
Easy-to-Use. Quickly get up and running in a familiar Orion web-based environment
Automated. Simple process from system set-up, end-point equilibration, and free energy calculation
Performance. Extremely fast and highly parallelizable; run an entire ligand dataset in a few hours
Control. Highly customizable for novice use and expert control
Integrated. Easily combine with other ligand- and structure-based methods

Rooted in Science, Optimized for Performance, Made for You

OpenEye delivers efficient and effective solutions to estimate binding free energies of protein-ligand complexes. Various options to suit your needs:

OE SZYBKI: An extremely fast approach to perform force field energy evaluations or geometry optimizations on small molecule ligands or protein-ligand complexes
OE Affinity Scoring: A fast, more approximate option that combines physics- and knowledge-based scoring. Automated for ease-of-use, OE Affinity Scoring provides you with quick relative binding free energy estimates from short-trajectory molecular dynamics (MD) trajectories
OE Affinity Relative Binding: A robust and accurate thermodynamic method to calculate relative binding free energies. Adapted from the Non Equilibrium Switching (NES) work published from the Max Planck Institute, OpenEye has improved the methodology and performance.

Our comprehensive solution ensure you get the benefit of speed, performance, and accuracy while saving time and money.

OpenEye offers automated, turn-key scientific solutions for various methodologies to meet all your binding affinity prediction needs.

OpenEye's Induced Fit Posing yields intuitive results that assist scientists in selecting high-quality candidates. An illustrative example is provided for its results against the CDK2 protein target.

Schematic depiction of OpenEye's Induced Fit Posing.

Induced Fit Posing

Predicting the binding of diverse ligands becomes notably challenging when adjustments are necessary in the receptor’s binding site. OpenEye’s Induced-fit posing (IFP) offers a specialized solution for accurate binding pose prediction in these scenarios. IFP predicts binding configuration of ligands that impact receptor’s binding site residue side chains. Use IFP to gain insights into the binding mechanisms of your compounds with flexible target sites and streamline selection of your lead compounds for optimization.

To enhance your ability to predict ligand binding affinity for proteins with flexible target sites, consider leveraging both IFP and OE Affinity Relative Binding. These tools combined help provide more accurate predictions of ligand-protein binding.

Download OpenEye Science Brief on Accurate Binding Pose Prediction with Induced-fit posing (IFP)

OpenEye provides a fully automated workflow to simplify your calculations; from protein-ligand preparation to analyzing Free Energies Results. The workflow is also customizable for experts use and control.

FAQs

: 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.

With version 2024.1, 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.
: 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.

Learn More

OE Affinity can help you estimate relative binding free energies, speed up your drug-design process, and save costs by reducing failure rates.

Download OpenEye Science Brief on Affinity (Free Energy) Prediction in Structure-Based Lead Optimization

Download OpenEye Science Brief on Accurate Binding Pose Prediction with Induced-fit posing (IFP)

For science details, WATCH OpenEye’s miniWebinar recording from September 2021 on Using Non Equilibrium Switching for your Relative Binding Free Energies Calculations by Christopher Bayly, Ph.D.

And WATCH the OE Affinity Mapper feature presented by Gaetano Calabro, Ph.D, from June 2022