- CONFLEX Previous version
CONFLEX 6 What's NEW
- 32/64 bit version and multi-core support
- You can now choose to install the 32/64 bit version according to your PC environment.
- Multi-core/multi-thread support for optimization of large molecules. You can specify the number of cores to be used when running the program. However, please use Parallel CONFLEX for distributed processing of alignment search.
- Crystal packing of conformers
- Replace amino acid residues
- Solvent Effect CONFLEX can now calculate the energy using the Generalized Born solvent model (GB/SA).
- Force Field options
Users can add the quasi-interaction effect to the force field. Users can also include additional restraints to specify the structural information.
- Point Charge
Users can define the point charge on each atom.
For Gaussian users, one can apply the partial charge calculated by Gaussian, and estimate the electrostatic interactions.
- Geometry Optimization options
- Switch between FAST and PRECISE Structure Optimization
- Convergence and Iteration
Users can specify the convergence criteria and iteration count for each optimization method.
- Conformation Search Option
CONFLEX recognizes the R/S configurations of chiral atoms and E/Z of double bonds. Users can now add your own absolute configuration of atoms.
- Peptide Bond Option
CONFLEX recognizes the rotatable bonds and add these to the stepwise rotation list. Users can exclude the peptide bonds(CO-NH), phi-psi bonds (CONH-Ca-CONH) or side chain bonds from a stepwise rotation list.
- Normal Mode Dynamics Analysis
By combining multiple vibrational mode, CONFLEX analyzes molecular dynamics. This enables users to analyze a reaction or folding path etc.
- Molecular force field
- Multi-threading with OpenMP was partially implemented. On machines with multi-core CPUs, the performance of structural optimization, etc. has been improved.
- An option to optimize only the positions of hydrogen atoms has been added. When combined with the previously introduced automatic hydrogen atom addition function, this is useful for crystal structure utilization.
- In order to handle molecules containing elements whose charge numbers are difficult to handle classically in force field calculations, it is now possible to set the charge number of the specified atom.
- The method of calculating the electrostatic interaction energy can be changed to the method used for other force fields.。
- Conformation Search
- Selective specification of the structural perturbation methods FLAP/FLIP/SROT for substructure alignment search is now easily available.
- Pseudo Force calculations using Half-Harmonic and Morse functions have been introduced to optimize the structure and search for conformations by restricting the distance between atoms based on NMR-NOE information.
- Steric Coordination Analysis Function
- We have introduced a new method for calculating NMR coupling constants (3JHHM) using the Imai-Karplus formula
- Crystal calculation
- An option to extend the unit lattice, which is the entity ensemble for crystal calculations, has been added. By specifying this option, crystal calculations with extended lattices (supercells) as the entity ensemble can be easily performed.
- When using CIF format molecular structure files, the bond order and atomic charge can now be specified.
- It is now possible to set the bond length associated with an atom specified by its serial number or atomic number to an arbitrary length.
- The bond length of hydrogen atoms can now be modified to the standard bond length of the specified force field.
- Solvent Effect
- We have determined the solvent effect parameters of octanol. This allows us to optimize the structure using octanol as a solvent.
- LogP automatic calculation function is added. It automatically calculates the solvent effect of water and octanol.
- The calculation method and parameters of the solvent contactable surface area (SA) calculation have been improved.
- The vdW radius calculation method used for GB/SA calculations has been improved.
- Improved crystal calculations
- The parallel processing of crystal calculations has been completely improved.
- Crystal energy calculation and crystal structure optimization have been modified to perform parallel distributed processing.
- The analytical derivative of the intermolecular interaction energy is now available for all space groups.
- Fixed a problem in which the analytical derivative of the intermolecular interaction energy could not be obtained correctly for some space groups.
- In the case of structural optimization of an isolated system using a CMF molecular structure file as input, various outputs were generated after superimposing all atoms of the optimized structure and the input structure, but this has been changed to superimposing only heavy atoms.
- When outputting the vdW interaction and electrostatic interaction energies, the sum of the energies only in the Unit Cell where the original molecule exists was being output. This has been changed to output the total vdW interaction and total electrostatic interaction energies, respectively, which are the target of the crystal calculation. The lattice energy is defined as the sum of these energies.
- Fixed a problem in which the total number of atoms output was incorrect when the original molecule contained multiple molecules.
- Simplified Homology Modeling
- Given an input molecular structure in a PDB format file, simple homology modeling can now be performed.
- Improving the force field
- Added the ability to automatically generate torsion angle parameters.
- Users can now specify the atom type.
- The cross terms associated with bond stretch in MM2, EMM2, and MM3 have been modified to apply an electromegativity correction.
- Fixed a problem where parameter corrections for expansion and contraction due to chemical effects were not applied correctly in the MM3 force field.
- Corrected an error that occurred when performing calculations for Fe and Zn ion complexes.
- Many parameters for MMFF94s have been added.
- Conformation Search
- Fixed a problem that occurred when performing a parallel conformation search for a molecule that does not have a conformation isomer.
- Geometry optimization and vibration analysis calculations incorporating solvent effects (MMFF94s)
- Calculations using the GB/SA model have been extended to include geometry optimization, vibrational analysis, and conformational analysis (CONFLEX5 could only evaluate solvent effects on the initial structure or the optimized structure in vacuum). The available molecular force field is MMFF94s.
- It automatically optimizes the structure in the gas phase and in the solvent, and calculates the stabilization energy by solvation from the energy obtained by each optimization. The solvation stabilization energy can be calculated from the energy obtained from each optimization.
- Crystal structure optimization
- Based on CONFLEX's proprietary algorithm, crystal structure calculations can now be performed for organic compounds with known X-ray crystal structures, allowing for the optimization of various crystal structures originating from differences in conformational isomerism and molecular orientation. This makes it easy to study the energy evaluation of crystal polymorphs. Also, if the crystal structures of analogous compounds are known, it is possible to calculate unknown crystal structures.
- Addition of amino acid residue substitution function: PDB file option
- CONFLEX can now replace user-specified amino acid residues with any essential amino acid residues, provided that the input file is a Protein Data Bank (PDB) file format (.pdb file). This “amino acid residue substitution function” allows the user to change the primary sequence of a protein with a known structure, similar to homology modeling.
- In some PDB submissions, the coordinate information of side chain atoms of some amino acid residues is missing. We have added an error message when CONFLEX is run with such incomplete PDB registration data as input structure file. In addition, by using the newly added “Amino Acid Residue Replacement” function, the missing amino acid residue's side chain atom coordinates can be generated and the correct molecular structure calculation can be performed.
- Add conformation search option.
- It is now possible to specify the number of Stepwise Rotation steps for bonds that are expected to have rotational isomers. This makes it possible to perform limited coordination searches for polymeric materials and biomacromolecules. However, care should be taken when analyzing the resulting isomers, as this method does not allow for sufficient coordination search.
- Addition of force field parameters for MMFF94s
- We have added the force field parameters for MMFF94s that we developed. This increases the number of molecular species that can be calculated in the MMFF94s force field.
- Frontier Mode Tracking (FMF) Method (Coordinate Transformation Transition State Search)
- In order to search for the transition state of the conformation transformation, we have introduced our own frontier vibration mode tracking method. However, its use is limited at present.
CONFLEX 5 What's NEW
Solvent effect calculations using the Generalized Born Method (GB/SA) have been added.
- After the usual structure optimization, we can now use the GB/SA method to analyze the structure and estimate the solvent effect.
- The solvents that can be used are currently “water” and “octanol”.
D. Q. Peter, S. Shenkin, F. P. Hollinger, W. C. Still,
J. Phys. Chem. A, 1997, 101, 3005-3014.
S. A. Best, K. M. Merz Jr., C. H. Reynolds,
J. Phys. Chem.B, 1997, 101, 10479-10487.
A. Cheng, S. A. Best, K. M. Merz Jr., C. H. Reynolds,
J. Mol. Graph. Mod., 2000, 18, 273-282.
Force Field option
Pseudo forces can now be added to the force field used for structural optimization. Users can now add forces to the potentials used to calculate the force field energy. This can be used to fix a part of a structure. The following items can be applied
- Bond length between two atoms
- Distance between two unbonded atoms
- Bond angle between three atoms
- Dihedral angle between four atoms
- Out-of-plane angle between four atoms
- Phase angle of 5-membered ring
Geometry optimization options
Geometry optimization options “FAST” and “PRECISE” have been added.
- “FAST” is intended for large molecules, and the method uses Conjugate gradient, with loose convergence conditions.
- If “PRECISE” is specified, the Steepest Descent → Conjugate gradient → Full-matrix Newton-Raphson methods are used to optimize the system.
Conformation Search Options
It is now possible to add user-specified absolute configuration and geometric isomer checks to the automatically added chiral center absolute configuration (R/S) and double bond geometric isomer (E/Z) checks.
This allows you to exclude numbering-dependent isomerization into pseudo-chiral and pseudo-geometric isomers that may have occurred in the past during coordination searches.
Exclude peptide bonds (CO-NH) from the bond rotation list
Peptide bonds (CO-NH), φψ bonds (CONH-Cα-CONH), and side chains (all bonds except peptide bonds and φψ bonds) can now be selectively excluded from the Stepwise Rotation In particular, the torsion angles of peptide bonds can now be selectively excluded from the list of bond rotations by Stepwise Rotation. In particular, the torsion angles of peptide bonds can be checked for geometric isomers, so that the initial structure of s-cis/trans can be retained in the coordination search. In addition, by combining these functions, it is now possible to search for peptide chain backbone only or residue side chains only.
Vibration dynamics analysis function
A new vibration kinetics analysis function has been added. By synthesizing not only single vibrational modes but also multiple vibrational modes, it is possible to perform configuration-dependent kinetic analysis, which can be used for initial analysis of reactions and folding pathways.