CONFLEX Manual

Geometry Optimization Keywords

Keyword	Options	Description
OPT= Default: full-matrix Newton-Raphson Method (NEWTON) Example: OPT=CONGRD		Geometry optimization method
	STEEPD	steepest descent method
	CONGRD	conjugate gradient method
	VARMET	variable metric method
	NEWTON	full-matrix Newton-Raphson method
	NONE	In the case of “OPT=NONE”, only energy calculation will be performed for the input structure.
	FAST	“FAST” is a special setting for large molecule. This is corresponding to the following keywords: “OPT=CONGRD TG=1.0 GCONV_CG=1.0D-3 XCONV_CG=1.0D-4”
	PRECISE	“PRECISE” is a sequential procedure of STEEPD, CONGRD, and NEWTON. When this option is selected, some convergence criterion set to the following values: “TG=1.0 GCONV_CG=1.0D-3 XCONV_CG=1.0D-4 GCONV_NR=1.0D-6 XCONV_NR=1.0D-6”
	FMF	frontier mode following method (FMF) FMF method is one of the transition state search method based on a similar technique of the eigen vectors following method.
	GROUP	Molecular Object Optimization Method
IRC_FMF=	n	FMF method follows the n-th eigenvector. Default is “1”, which means that it searches for the corresponding transition state along the first eigenvector.
NOOPT		Only energy calculation will be performed for the input structure. This keyword corresponds to “OPT=NONE”
OPTBY= Example: OPTBY=GRADIENT	ENERGY GRADIENT	Objective function to be minimized during geometry optimization. Default is “ENERGY”
TG= Example: TG=2.5	ff.ff	Gradient threshold for pre-optimization (steepest descent Method). By default, TG is set to 5.0 kcal/mol/Å
GCNVRG= Example: GCNVRG=1.0E-5	ff.ff	Threshold of gradient convergence for geometry optimization. By default, GCNVRG is set to 1.0E-6 kcal/mol/Å
XCNVRG= Example: XCNVRG=1.0E-5	ff.ff	Threshold of atom displacement convergence for geometry optimization. By default, XCNVRG is set to 1.0E-6 kcal/mol/Å
STEEPD= CONGRD= VARMET= NEWTON=	(Gconverg,Xconverg)	Threshold of energy gradient (Gconverg) and atom displacement (Xconverg) convergence for geometry optimization by using each method.
MAXITR_SD= MAXITR_CG= MAXITR_VM= MAXITR_NR=	n	Maximum number of iterations for geometry optimization. _SD for steepest decent, _CG for conjugated gradient, _VM for variable metric, and _NR for Newton-Raphson method.
NOSYMMETRY NOSYMMETRY=	ON OFF	Set whether the coordinate transformation of molecular structure for analyzing the symmetry is performed or not. NOSYMMETRY=OFF: Do the coordinate transformation and ana- lyze the symmetry during optimization. NOSYMMETRY or NOSYMMETRY=ON: Do the optimization without the coordinate transformation. Default: NOSYMMETRY=OFF
FIXED_ATOMS= Example: FIXED_ATOMS=(1,3,5-8) fixes atoms No. 1, 3, 5, 6, 7, and 8.	(n1,n2,n3-n4,...)	Fix specified atoms (n1, n2, etc) during optimization. When a hyphen is inserted like n3-n4, all the atoms from n3 to n4 are fixed. “NOSYMMETRY=ON” is set implicitly.
OPTMZD_ATOMS= Example: OPTMZD_ATOMS=(2,4,9-11) optimizes atoms No. 2, 4, 9, 10, and 11	(n1,n2,n3-n4,...)	Optimize specified atoms (n1, n2, etc) and fix the others during optimization. When a hyphen is inserted like n3-n4, all the atoms from n3 to n4 are optimized. “NOSYMMETRY=ON” is set implicitly. Note: When the keywords “FIXED_ATOMS=” and “OPTMZD_ATOMS=“ are set at the same calculation, both are invalidated and the optimization of all atoms is performed.

CONFLEX Conformation search keywords

Keyword	Options	Description
CONFLEX		Conformation search will be performed.
SEL= Example: SEL=1.0 SEARCH=ENERGY	ff.ff	The value of “SEL” defines the search limit that controls the range from which the initial structures are selected. If the value of “SEARCH” is “ENERGY”, the search limit is defined in kcal/mol, and if “BOLTZ”, the search limit is defined in % population according to Boltzmann distribution. By default, this value is set to 1 kcal/mol. See also “SEARCH=”
SEARCH= Example: SEARCH=ENERGY	ENERGY BOLTZ	Definition of the evaluation unit for the search limit. If the value of “SEARCH=” is “ENERGY”, the search limit is defined in kcal/mol, and if “BOLTZ”, the search limit is defined in % population according to Boltzmann distribution. By default, this value is set to “ENERGY”. See also “SEL=”.
MAXINIT= MAXSTACK= Example: MAXINIT=4	n	Number of the initial structures used for a generating process of trial structures.
MAXCYCLE=	n	Number of search cycles is fixed. In general, the number of search cycles can not defined by user, because of SEL value control (see “SEL=”). This keyword, that forcibly sets the limit of search cycles, should be used only for evaluating an time-consuming of the practical conformation search.
ADD_CONFIG_RS=	I	Tetrahedral configuration around the I-th centre atom can be fixed during CONFLEX search, even if the I-th atom is not chiral center of atom.
ADD_CONFIG_EZ=	(I,J,K,L)	Torsional configuration defined by I-J-K-L dihedral angle can be fixed during CONFLEX search, even if the J-K bond is not double bond.
DELETE_CONFIG_EZ=	(I,J,K,L)	Automatically fixed torsional configuration around I-J-K-L during conformation search can be released.
FLAP		If the corner-flapping perturbation is possible, it will be performed.
NOFLAP		The corner-flapping perturbation is prohibited, even if it is possible.
FLAP_SELECT=	I	User can specify a flapping atom as the I-th atom. When this option is used, flapping atom list, which is automatically determined, must be ignored.
FLAP_DESELECT=	I	User can remove the I-th atom from the flapping atom list, which is automatically deter- mined. The specified I-th atom is prohibited from flapping perturbation.
FLIP		If the edge-flipping perturbation is possible, it will be performed.
NOFLIP		The edge-flipping perturbation is prohibited, even if it is possible.
FLIP_SELECT=	(I,J)	User can specify a flipping bond between the I-th and J-th atoms. When this option is used, flipping bond list, which is automatically determined, must be ignored.
FLIP_DESELECT=	(I,J)	User can remove the I-J bond from the flipping bond list, which is automatically determined. The specified I-J bond is prohibited from flipping perturbation.
SROT		If the stepwise rotation perturbation is possible, it will be performed.
FIXED_SROT_NSTEP=	n	Number of rotational isomers expected in stepwise rotation for a bond is fixed to n. (n-1) trial structures will be generated from each of the initial structures.
NOSROT		The stepwise rotation perturbation is prohibited, even if it is possible.
SROT_SELECT=	(I,J,N)	User can specify a stepwise rotatable bond between the I-th and J-th atoms and rotation angle of 360/N°. When this option is used, SROT torsional bond list, which is automatically determined, must be ignored.
SROT_DESELECT=	(I,J)	User can remove the central I-J bond from the SROT torsional bond list, which is automatically determined. The specified I-J bond is prohibited from stepwise rotational perturbation.
SROT_ADD=	(I,J,K,L,N)	User can add I-J-K-L torsional configuration and rotation angle of 360/N° into the SROT list even that J-K is double bond.
XSROT_PEPTIDE_BOND		All peptide bonds (CO-NH) of the molecule are removed from SROT list, and their s-cis/trans stereo-configurations will be kept the initial situation during CONFLEX search.
CHECK= Example: CHECK=(XCORD,HEAVY)		This keyword defines the conformational similarity indices. In conformational space search, the program must check the conformation redundancy of the newly optimized structures with the already-known structures stored in conformation database. In CONFLEX, the po- tential energy values are always used in this purpose, because the severe full-matrix Newton optimization can reach to 1.0D-6 kcal/mol/Å. In scarce cases, however, the energy does not work enough for the correct distinction of conformation. That is why the follow- ing similarity indices are prepared for the additional comparison between two conformers:
	XCORD	The difference of the molecular atomic coordinates that are reoriented to a standard orientation based on the moment of inertia is directly compared.
	TORSION	The sum of Root-mean-square differences in the corresponding pair of torsion angles of skeleton bonds is compared.
	MOMENT	The difference of the axis components in the moment of inertia is compared.
	NOENERGY	Those additional comparisons without the potential energy comparison are performed. Otherwise, the energy check is always performed.
	HEAVY	Positions of all hydrogens will be ignored in XCORD comparison.
ESAV= Example: ESAV=6.5	ff.ff	Defines the highest potential energy (EGYMAX) of the stored conformer: EGYMAX = ESAV + the potential energy of the global energy-minimum conformer (GEM). By default, ESAV is set to N/2 kcal/mol (N = total number of atoms in the molecule). Those conformers having the relative potential energies smaller than ESAV from the GEM, are stored into the conformation database, but those having potential energy higher than EGYMAX are discarded. The efficiency and the reliability of CONFLEX search is greatly influenced by the number of stored structures. A small ESAV leads to a smaller number of stored structures and less computer time, but the risk of missing significant conformers increases. This is because unstable conformers sometimes produce stable conformers upon local perturbation. On the other hand, a large ESAV ensures finding all significant conformers but leads to longer calculation time.
EDIF_HARD= Example: EDIF_HARD=1.0D-5	ff.ff	Threshold of the basic comparison in potential energies if “CHECK=NOENERGY” is not specified. See also “CHECK=”.
EDIF_LOOSE= Example: EDIF_LOOSE=2.0	ff.ff	Threshold for the comparison of potential energies in the first stage of redundancy test when “CHECK=XCORD” or “CHECK=TORSION” is specified. If a new conformer has the same potential energy, within this range, with one of the stored structures, the program proceeds to the torsion angles test. The default is 3N/100 kcal/mol.
GRMS_HARD= Example: GRMS_HARD=1.0D-5	ff.ff	One of the thresholds for the RMS average of the final gradient for the termination of the geometry optimization.
GRMS_LOOSE= Example: GRMS_LOOSE=1.0D-7	ff.ff
XCOD_MAX= Example: XCOD_MAX=1.0	ff.ff	Set the threshold for comparing the maximum difference in Cartesian coordinates between the conformations when the “CHECK=XCORD” is specified
XCOD_RMS= Example: XCOD_RMS=4.0	ff.ff	Set the threshold for comparing the RMS value of the difference in Cartesian coordinates between the conformations when the “CHECK=XCORD” is specified.
TORS_MAX= Example: TORS_MAX=1.0D-2	ff.ff	Set the threshold for comparing the maximum value of the difference in torsion angles between the conformations when the “CHECK=TORSION” is specified.
TORS_RMS= Example: TORS_RMS=1.0D-1	ff.ff	Set the threshold for comparing the RMS value of the difference in torsion angles between the conformations when the “CHECK=TORSION”
MOMT_MAX= Example: MOMT_MAX=0.5	ff.ff	Set a threshold to compare the maximum difference in the components of the moment of inertia between the conformations when “CHECK=MOMENT” is specified.
MOMT_RMS= Example: MOMT_RMS=0.1	ff.ff	Set a threshold value to compare the RMS value of the difference in the components of the moment of inertia between the conformations when “CHECK=MOMENT” is specified.