Global-MMX (GMMX) is a steric energy minimization program which uses any of the supported force fields (MMX, MM3, MMFF94, and Oplsaa) and operates in batch mode to search conformational space and to list the lowest energy unique conformations found.
One of the major problems in molecular modeling is known as the local minimum energy problem. Energy minimization routines are designed to remove energy from the system by proceeding downhill on the potential energy surface. Invariably such routines find the local energy minimum closest to the input geometry. The local energy minimum may not be the global energy minimum on the potential energy surface. Information about the number and energies of local energy minima can be important in planning syntheses, understanding reactions mechanisms and interpreting NMR spectra. GMMX is designed to address the local energy minimum problem by automating the generation, minimization and comparison of conformations.
Conformational searching in GMMX is a two part process. The first part involves setting up the calculation. The user is prompted for the name of the structure file (presumably generated with PCMODEL), whether the search should be done in cartesian space, dihedral space or both, the number, size and atom numbers of any rings to search, and then the number of rotatable bonds and the atom numbers of each of the bonds. In addition there are many user-defineable options, such as the energy window for keeping conformations, how comparisons are done, whether to maintain stereochemistry, when to stop the calculation and whether to query the final structures for distances, angles, dihedrals or NMR coupling constants. All of this information is collected by prompting the user. If the user does not have a preference then there are reasonable defaults built into GMMX and the user need only select the defaults. Setting up the calculation usually takes only a few minutes. Then GMMX starts and the setup instructions are read and the calculations started. New conformations are generated, checked for bad 1,5 van der waals interactions, double bond isomerization, loss of sterochemistry and other problems and then minimized using the MMX force field. The minimized structure is compared against all other structures previously minimized to detect duplicates, and if the structure is unique and within the energy window it is saved. As the calculation proceeds the number of accepted structures, the total number of structures examined, the number of duplicates and the time of the calculation are reported to the screen. The calculation may be paused and restarted at any time, and it may also be stopped manually. When the calculation ends normally all the structures that were collected are sorted by energy and those that still fall within the energy window are written to a file. These structures can then be examined in PCMODEL, or they can be analyzed with a comparison program that accompanies GMMX.
There are several other methods for attacking the local energy minimum
problem. GMMX uses a stochastic process to generate new starting conformations.
As such there is no guarantee that the global energy conformation will be found
nor that the same path will be followed if the calculation is rerun. For very
small molecules with only a few rotatable bonds a GRID search (dihedral driver
) calculation would be faster than GMMX. However grid searches are factorially
complex problems and the number of required calculations becomes unreasonable
as the number of rotatable bonds increases. Another alternative method for
solving the local energy minimum problem would be molecular dynamics(MD). In
this method the atoms are given some initial velocity and their progress is
then followed over time as the atoms move according to
New in version 1.5.
GMMX is available for :
Price $600 list, $400 academic
Bloomington, IN 47402-3076