8 February 2019
Molecular Modeling and Structure-based Drug Design Systems
- The Full-Automatic, GUI-Based Molecular Structure 2D-3D Converter -
Mol Dimension is a molecular 2D-3D structure conversion program for preparing the 3D structure of compounds in a 2D structure database, using HyperChem program.* The program can automatically and sequentially construct the 3D structure of the corresponding 2D structure with the atomic type of a desired force field and the Mulliken atomic charges obtained from the semi-empirical calculations. The program can be used for preparing a 3D structure database of compounds which are managed as a 2D structure database such as an in-house compound database, vender database, and commercial database, using a database manager such as ChemFinder** and ISIS/base programs.***
Additionally, file format of 3D structures which obtained from third-party 2D-3D converters such as OpenBabel, CORINA, and OMEGA can be simply converted for Docking Study module program.
Mol Dimension carries out file separation function of single big multiple compound SDF and MOL2 files, 3D compound database construction function having the desired atomic type and Mulliken atomic charges, and Rule of 5, so that Mol Dimension is useful for construction of compound database for third-party docking programs.
Docking Study with HyperChem and Virtual Screening System developed on the basis of Docking Study with HyperChem can perform the in-silico screenings for the 3D structure database converted by the Mol Dimension program.
This program is packaged into Docking Study with HyperChem and the corresponding cluster version is packaged into Virtual Screening System. Once you prepare a 2D structure of compound(s) in a SDF, an RDF (MDL), or MOL2 (Tripos) format, all other processes such as a file management are automatically controlled by the program. Additionally, these packages can use a desired compound ID such as MOL ID, CAS NO, Vender Code, and File Name to operate consistently the compound through all module programs. Thus, you can easily return to the corresponding 2D structure from the hit compounds.
Mol Dimension has AutoDock Vina In Silico Screenings Interface, which can automatically construct a compound database in AutoDock PDBQT format from SDF and MOL2 formats and continuously screen the compound database using AutoDock Vina program.****
Thus, combination between Docking Study program and AutoDock Vina program can be used for effectively obtaining a drug candidate.
**** Note that AutoDock Vina program is different docking program from Docking Study with HyperChem. Docking Study with HyperChem can only provide the useful GUI environment for performing the AutoDock Vina in silico screenings.
The following scheme is a series of the structural conversions for a single compound in the core of the Mol Dimension program.
Read 2D Structure (first molecule in the file) > Assign Possible Hamiltonians > Assign Chiral Centers and Double Bonds > Generate All Isomers (option, double bond and amide bond are able to fix to each of cis and trans configurations) > Set Constraints (e.g., Chiral Center) > Three-dimensionalize > Remove Constraints > Add Hydrogens > Ionize (option: carboxylic acid, sulfonic acid, phosphoric acid, and guanidino group) > Assign Total Charges and Spin Multiplicity > Set Restraints (option: amide bond) > Optimize Geometry Using MM+ Force Field Calculation (bond dipoles condition; option: convergence conditions; single point calculation is also available) > Remove Restraints > Optimize Geometry Using a Desired Semi-empirical Quantum Mechanics Calculation (CNDO, INDO, MINDO3, MNDO, MNDO/d, AM1, or PM3; option: convergence conditions; single point calculation is also available) > Assign Mulliken Atom Charges > Set a Desired Force Field Condition (Amber94, Amber96, Amber99, CHARMM19, CHARMM22, CHARMM27, OPLS, or MM+) > Assign Force Field Atom Types > Save Structure
A molecular browser, Mol Browser, can be used for browsing structures converted by the Mol Dimension program. Mol Browser can also update and browse structures under the background 2D-3D structural conversions with the Mol Dimension program. Mol Browser is useful for browsing a large number of small molecules in a 3D structure database prepared by the Mol Dimension program.
* HyperChem is a registered trademark of Hypercube, Inc.
** ChemFinder is a registered trademark of CambridgeSoft, Corporation.
*** ISIS base is a registered trademark of Elsevier MDL, Inc.