VConf

VConf, developed by VeraChem LLC, is a powerful and flexible 2D-to-3D conversion and conformational search application designed for processing drug-like compounds. It accepts an SD file of molecules in arbitrary initial conformations — whether 2D or low-grade 3D — and generates high-quality 3D structures across a range of low-energy conformations. A key feature is its symmetry-aware output filter, which ensures that no duplicate conformations appear in the results. VConf is available as a command-line driven application for Linux and Microsoft Windows.

VConf is well suited for computational chemists and drug discovery teams who need to prepare compound libraries for downstream calculations such as molecular docking, or who require thorough conformational sampling of small molecules.

Modes of Operation

• 2D to 3D with multiple ring conformations (Prep mode): Quickly transforms a 2D or low-grade 3D starting conformation into several high-quality 3D structures, generating various conformations of any flexible rings present. This mode is particularly useful for preparing molecules for subsequent calculations, such as docking, which vary only bond torsions.
• Full conformational search (Search mode): Carries out the prep step described above and then executes a Tork conformational search across all degrees of freedom. Time requirements vary depending on molecular complexity and the options selected by the user.

How VConf Works

1. Small disconnected molecular fragments are removed from the input molecule, and missing hydrogens or formal charges are added.
2. Ring systems are detected, and multiple low-energy conformations of each ring system are drawn from a dynamic ring database. For rings not already in the database, Tork is used to quickly build conformations.
3. Multiple starting conformations of the molecule are built around these rings and relaxed using a brief Monte Carlo run followed by energy minimization.
4. In prep mode, the calculation stops at this point. In search mode, the resulting structures are used to initiate Tork searches to generate a broader range of low-energy conformations.
5. Tork uses normal modes in internal coordinates to efficiently identify productive directions for the conformational search.
6. Generated conformations are checked for correct chirality and cis/trans conformations at double bonds.
7. Repeat conformations are eliminated with correction for molecular symmetries, and successful conformations are written to output.

Energies are calculated using a tuned version of the Dreiding force field, combined with VeraChem's partial atomic charges (as provided by VCharge) and a distance-dependent dielectric model.

User-Configurable Options

• Specification of atoms whose positions will be locked to their input coordinates
• Maximum number of output structures
• Energy cutoff for filtering out high-energy structures
• Distance tolerance for filtering repeat structures
• Constraints on the chirality of stereocenters and on cis/trans conformations at double bonds
• Method for determining atom chirality: parity field in the atom block, stereo bond information in the bond block, or coordinates of the input structure (multiple methods can be specified)
• Valence detection method: based on formal charges specified in the input SD file, or on the assumption that all intended hydrogens are present in the input SD file
• Distance-dependent dielectric constant coefficient

Windows Graphical User Interface

• The MS Windows version of VConf includes a graphical user interface that facilitates assigning parameters, running VConf, and viewing results.
• The interface integrates VConf with VDisplay, VeraChem's molecular display program, along with helpful VConf support utilities.
• The command-line version is also available for Linux environments.

VConf is part of VeraChem's broader suite of small molecule tools, which includes VDraw, VMap, VCharge, VFilter, Vrms, and VDisplay. The underlying Tork conformational search algorithm is documented in peer-reviewed literature, and the symmetry-correction methodology is grounded in published research on the identification of topological and 3D molecular symmetries.