VM2

VM2 is VeraChem LLC's advanced computational chemistry software package designed for accurate protein-ligand and host-guest binding free energy prediction. Built on a rigorous statistical thermodynamics framework, VM2 is positioned as the most advanced end-point free energy method in routine use today, making it an essential tool for computational chemists and drug discovery teams engaged in lead optimization and ligand series ranking.

Unlike traditional scoring or docking approaches, VM2 treats both binding sites and ligands as fully flexible, incorporates solvation and entropic terms, and employs efficient conformational search algorithms to deliver binding affinity predictions that go well beyond simple docking scores. The latest version of VM2 supports parallel processing via MPI, OpenMP, and CUDA, enabling fast multi-CPU and multi-GPU calculations at scale.

True Free Energy Calculations

• Provides true free energies rather than approximate scoring, delivering more accurate protein-ligand affinity predictions
• Includes both configurational and conformational entropy contributions
• Accounts for anharmonic effects that simpler methods ignore

Fully Flexible Ligand and Protein Treatment

• Fully mobile receptor region is treated as essential for accurate pose and affinity prediction
• Protein backbone is fully flexible, as are side chains
• Users can selectively define regions of the protein as mobile or fixed according to their requirements

Handling of Diverse Ligand Sets

• Unlike free energy perturbation (FEP) methods, VM2 can easily accommodate arbitrary changes to ligand functional groups
• Can efficiently incorporate prior system information such as known binding poses when available
• Capable of determining binding poses with no prior knowledge when required

Highly Efficient Conformational Searching

• Conformational search engine reliably finds low-energy minima of large molecular systems
• Employs novel distort-minimize algorithms for thorough conformational sampling
• Uses distortions along linear combinations of torsional modes
• Includes rigid body rotation-translation searching to identify all significant binding modes, not just a single pose

Fast and Accurate Solvation

• Applies Poisson-Boltzmann Surface Area (PBSA) corrected potential energies for accurate solvation treatment
• Supports the inclusion of explicit water molecules in the binding site when required

Energy Decomposition and Binding Affinity Analysis

• Provides detailed energy decomposition to identify favorable and unfavorable free energy contributions from individual functional groups
• Helps guide ligand design decisions during lead optimization efforts
• Supports understanding of the system through comprehensive energy analysis

CloudVM2 — Cloud-Based Access

• VM2 has been ported to Amazon Web Services (AWS) and Google Cloud Platform for cloud-based computation
• Features an easy-to-use graphical interface for submitting VM2 calculations
• Enables fast turnaround by calculating affinities for an entire protein-ligand series concurrently

Multiple Energy Models and Licensing

• Supports multiple energy models to suit different use cases
• Flexible licensing options available for both commercial and academic users
• Results analysis is available through integration with Chemical Computing Group's MOE graphical user interface via the CCG SVL Exchange

VM2 is developed and distributed by VeraChem LLC and has been applied in peer-reviewed research including QM-VM2 studies of host-guest binding free energies published in the Journal of Chemical Physics. The software is suitable for both commercial drug discovery pipelines and academic research environments.