Vconf

Vconf is a powerful and flexible conformational search application which processes an SD file of drug-like compounds containing an initial 2D or 3D conformation of each molecule. It provides for two major modes of operation:

2D to 3D with multiple ring conformations
In "prep" mode Vconf quickly transforms a 2D or low-grade 3D starting conformation into several high-quality 3D structures with various conformations of any flexible rings that may be present. This mode is useful for preparing molecules for subsequent calculations, like docking, which vary only bond torsions.
Full conformational search
In "search" mode, Vconf carries out the "prep" step described above, and then executes a Tork conformational search in all degrees of freedom. Time requirements vary depending upon the complexity of the molecule and the options selected by the user.

User Options

Command-line options provide detailed user control, including:

list of atoms, if any, 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
whether constraints should be imposed on the chirality of stereo centers and on cis/trans conformations at double bonds
how the chirality of a atom should be determined; i.e. by the parity field in the atom block, the stereo bond information in the bond block, or the coordinates of the input structure. More than one method can be specified
how valence is detected; i.e. based on formal charges specified in input SDfile, or on the assumption that all intended hydrogens are present in the input SDfile
the distant dependent dielectric constant coefficient

How Vconf Works

The method begins by removing small disconnected molecular fragments from the input molecule and adding missing hydrogens or formal charges. Vconf then detects ring systems and draws multiple low-energy conformations of each ring system from a dynamic ring database or uses Tork to quickly build conformations of rings not already in the database. Multiple starting conformations of the molecule are then built around these rings and relaxed by a brief Monte Carlo run followed by energy minimization. In "prep" mode, the calculation is stopped at this point. In "search" mode, the resulting structures are used to initiate Tork searches to generate a range of low-energy conformations. As described in the first citation below, Tork uses normal modes in internal coordinates to efficiently identify productive directions for the conformational search. The conformations thus generated are checked for correct chirality, and cis/trans conformations at double bonds. Finally, repeat conformations are eliminated, correcting for symmetries, and the successful conformations are written to output. Energies are based upon a tuned version of the Dreiding force field, with VeraChem's partial atomic charges (see Vcharge) and a distance-dependent dielectric model..

Windows User-Interface
The MS Windows version of Vconf includes a convenient graphical user interface that facilitates assigning parameters, running Vconf, and viewing its results. The interface brings together Vconf, our molecular display program Vdisplay, and helpful Vconf support utilities, as shown in the following screen-shots. (Click images for full-sized views)

Vconf version 1.0 for MS Window2000/XP including a graphical user interface and Linux.

References

Main Citation

Tork: Conformational analysis method for molecules and complexes. Chang,C. and Gilson,M.K. J. Comput. Chem. 2003, 24:1987-1998.

Background Citations

Calculation of partial charges and resonance forms: Fast assignment of accurate partial atomic charges. An electronegativity equalization method that accounts for alternate resonance forms. Gilson,M.K., Gilson,H.S.R. & Potter,M.J.; J. Chem. Inf. Comput. Sci. 2003, 43(6), 1982-1997.

Identification of symmetries in molecules and complexes. Chen, W., Huang, J., & Gilson, M.K.; J. Chem. Inf. Comput. Sci., 2004, 44, 1301-1313.

Smallest set of simplest rings: Ring perception using breadth-first search. Figueras, J.; J. Chem. Inf. Comput. Sci.. 1996, 36(5), 986-991.

DREIDING: A generic force field for molecular simulation. Mayo, S.L., Olafson, B.D., & Goddard III, W. A.; J. Phys. Chem. 1990, (94), 8897-8909.

GAFF: http://amber.scripps.edu/ parameters from June 2003

Ligand-receptor docking with the Mining Minima optimizer. David, L., Luo,R. & Gilson, M.K. J. Comput. Aided Molec. Des. 2001, 15:157-171.

Enhanced docking with the mining minima optimizer: Acceleration and side-chain flexibility. Kairys,V. and Gilson,M.K. J. Comput. Chem. 2002, 23:1656-1670.