{+ file: optimize_rweight.inp +}
{+ directory: xtal_refine +}
{+ description: Optimize Rweight (xray/B-restraints weight) +}
{+ authors: Axel T. Brunger and Paul D. Adams +}
{+ copyright: Yale University +}

{+ reference: A.T. Brunger, The Free R Value: a Novel Statistical 
              Quantity for Assessing the Accuracy of Crystal 
              Structures, Nature 355, 472-474 (1992) +}

{- Guidelines for using this file:
   - all strings must be quoted by double-quotes
   - logical variables (true/false) are not quoted
   - do not remove any evaluate statements from the file 
   - the selections store1 through store8 are available for general use -}

{- begin block parameter definition -} define(

{============================ coordinates ============================}

{* coordinate file *}
{===>} coordinate_infile="amy.pdb";

{==================== molecular information ==========================}

{* topology files *}
{===>} topology_infile_1="CNS_TOPPAR:protein.top";
{===>} topology_infile_2="CNS_TOPPAR:dna-rna.top";
{===>} topology_infile_3="CNS_TOPPAR:water.top";
{===>} topology_infile_4="CNS_TOPPAR:ion.top";
{===>} topology_infile_5="CNS_TOPPAR:carbohydrate.top";
{===>} topology_infile_6="";
{===>} topology_infile_7="";
{===>} topology_infile_8="";

{* linkage files for linear, continuous polymers (protein, DNA, RNA) *}
{===>} link_infile_1="CNS_TOPPAR:protein.link";
{===>} link_infile_2="CNS_TOPPAR:dna-rna-pho.link";
{===>} link_infile_3="";

{* parameter files *}
{===>} parameter_infile_1="CNS_TOPPAR:protein_rep.param";
{===>} parameter_infile_2="CNS_TOPPAR:dna-rna_rep.param";
{===>} parameter_infile_3="CNS_TOPPAR:water_rep.param";
{===>} parameter_infile_4="CNS_TOPPAR:ion.param";
{===>} parameter_infile_5="CNS_TOPPAR:carbohydrate.param";
{===>} parameter_infile_6="";
{===>} parameter_infile_7="";
{===>} parameter_infile_8="";

{* molecular topology file: optional (leave blank for auto generation) *}
{* 
   Auto generation of the molecular topology from the coordinates should only 
   be used if:
   (1) Each distinct protein, DNA, or RNA chain must have a separate segid 
       (or chainid if the chainid is non-blank). 
   (2) Each contiguous protein, RNA, or RNA chain must not be disrupted by 
       other types of residues or ligands.  Rather, these other residues 
       should be listed after protein, RNA/DNA chains. 
   (3) Disulphides are automatically detected based on distances between the sulfur atoms
      (must be less than 3 A apart).
   (4) Broken protein/RNA/DNA chains without terminii must be more than 2.5 A apart to be recognized as such.
   (5) N-linked glycan links are automatically recognized if the bonded atoms are less than 2.5 A apart.
   (6) Automatic generation cannot be used with alternate conformations. 
   For ligands, the user must make suitable topology and parameter files.
   For non-standard covalent linkages, the custom patch file should be used.
   Alternatively, the generate.inp or generate_easy.inp task files
   can be used to generated the mtf prior to running this task file.
    *}
{===>} structure_infile="amy.mtf";

{* for auto generation: extra linkages and modifications by custom patches *}
{===>} patch_infile="";

{====================== crystallographic data ========================}

{* space group *}
{* use International Table conventions with subscripts substituted
   by parenthesis *}
{===>} sg="P2(1)2(1)2(1)";

{* unit cell parameters in Angstroms and degrees *}
{+ table: rows=1 "cell" cols=6 "a" "b" "c" "alpha" "beta" "gamma" +}
{===>} a=61.76;
{===>} b=40.73;
{===>} c=26.74;
{===>} alpha=90;
{===>} beta=90;
{===>} gamma=90;

{* anomalous f' f'' library file *}
{* If a file is not specified, no anomalous contribution will be included *}
{+ choice: "CNS_XRAYLIB:anom_cu.lib" "CNS_XRAYLIB:anom_mo.lib" "" user_file +}
{===>} anom_library="";

{* reflection files *}
{* specify non-anomalous reflection files before anomalous reflection files. *}
{* files must contain unique array names otherwise errors will occur *}
{===>} reflection_infile_1="amy.cv";
{===>} reflection_infile_2="";
{===>} reflection_infile_3="";
{===>} reflection_infile_4="";

{* reciprocal space array containing observed amplitudes: required *}
{===>} obs_f="fobs";

{* reciprocal space array containing sigma values for amplitudes: required *}
{===>} obs_sigf="sigma";

{* reciprocal space array containing test set for cross-validation: required *}
{===>} test_set="test";

{* number for selection of test reflections: required *}
{* ie. reflections with the test set array equal to this number will be
       used for cross-validation, all other reflections form the working set *}
{===>} test_flag=1;

{* reciprocal space array containing weighting scheme for observed
   amplitudes: optional *}
{* only used for the "residual" and "vector" targets - this will
   default to a constant value of 1 if array is not present *}
{===>} obs_w="";

{* reciprocal space array containing observed intensities: optional *}
{* required for the "mli" target *}
{===>} obs_i="";

{* reciprocal space array containing sigma values for intensities: optional *}
{* required for the "mli" target *}
{===>} obs_sigi="";

{* reciprocal space arrays with experimental phase probability
   distribution: optional *}
{* Hendrickson-Lattman coefficients A,B,C,D *}
{* required for the "mlhl" target *}
{+ table: rows=1 "HL coefficients" cols=4 "A" "B" "C" "D" +}
{===>} obs_pa="";
{===>} obs_pb="";
{===>} obs_pc="";
{===>} obs_pd="";

{* complex reciprocal space array containing experimental phases: optional *}
{* required for the "mixed" and "vector" targets *}
{===>} obs_phase="";

{* reciprocal space array containing experimental figures of merit: optional *}
{* required for the "mixed" target *}
{===>} obs_fom="";

{* resolution limits to be used in refinement *}
{* the full resolution range of observed data should be used in refinement.
   A bulk solvent correction should be applied to allow the use of low
   resolution terms. If no bulk solvent correction is applied, data must
   be truncated at a lower resolution limit of between 8 and 6 Angstrom. *}
{+ table: rows=1 "resolution" cols=2 "lowest" "highest" +}
{===>} low_res=500.0;
{===>} high_res=2.0;

{* apply rejection criteria to amplitudes or intensities *}
{+ choice: "amplitude" "intensity" +}
{===>} obs_type="amplitude";

{* Observed data cutoff criteria: applied to amplitudes or intensities *}
{* reflections with magnitude(Obs)/sigma < cutoff are rejected. *}
{===>} sigma_cut=0.0;

{* rms outlier cutoff: applied to amplitudes or intensities *}
{* reflections with magnitude(Obs) > cutoff*rms(Obs) will be rejected *}
{===>} obs_rms=10000;

{=================== non-crystallographic symmetry ===================}

{* NCS-restraints/constraints file *}
{* see auxiliary/ncs.def *}
{===>} ncs_infile="";

{============ overall B-factor and bulk solvent corrections ==========}

{* overall B-factor correction *}
{+ choice: "no" "isotropic" "anisotropic" +}
{===>} bscale="anisotropic";

{* bulk solvent correction *}
{* a mask is required around the molecule(s). The region
   outside this mask is the solvent region *}
{+ choice: true false +}
{===>} bulk_sol=true;

{* bulk solvent mask file *}
{* mask will be read from O type mask file if a name is given
   otherwise calculated from coordinates of selected atoms *}
{===>} bulk_mask_infile="";

{* automatic bulk solvent parameter optimization for e-density level sol_k (e/A^3) and B-factor sol_b (A^2) *}
{+ choice: true false +}
{===>} sol_auto=true;

{* fixed solvent parameters (used if the automatic option is turned off) *}
{+ table: rows=1 "bulk solvent" cols=2 "e-density level sol_k (e/A^3)" "B-factor sol_b (A^2) " +}
{===>} sol_k=0.3;
{===>} sol_b=50.0;

{* optional file with a listing of the results of the automatic bulk solvent optimization *}
{===>} sol_output="";

{* solvent mask parameters *}
{+ table: rows=1 "bulk solvent" cols=2 "probe radius (A) (usually set to 1)" "shrink radius (A) (usually set to 1)" +}
{===>} sol_rad=1.0;
{===>} sol_shrink=1.0;

{========================== atom selection ===========================}

{* select atoms to be included *}
{===>} atom_select=(known and not hydrogen);

{* select atoms whose B-factors will remain fixed *}
{===>} atom_fixed=(none);

{* select main chain atoms for target sigma assignment *}
{* note: atoms outside this selection will be considered to be
   side chain atoms *}
{===>} atom_main=(name ca or name n or name c or name o or name ot+);

{================ B-factor minimization parameters ===================}

{* reset all atomic B factors to this number if positive *}
{===>} reset_b=-1;

{* number of steps of restrained individual B-factor minimization *}
{===>} bfactor_nstep=15;

{* initial weight for B-factor restraints *}
{* if -1, the weight will be automatically determined. *}
{===>} rweight=-1;

{* minimum and maximum allowed B-factor *}
{===>} bmin=1;
{===>} bmax=900;

{* target sigma values for restrained B-factor refinement *}

{* mainchain bonds *}
{===>} bsig_main=1.5;
{* mainchain angles *}
{===>} asig_main=2.0;

{* sidechain bonds *}
{===>} bsig_side=2.0;
{* sidechain angles *}
{===>} asig_side=2.5;

{* refinement target *}
{+ list: mlf: maximum likelihood target using amplitudes
         mli: maximum likelihood target using intensities
        mlhl: maximum likelihood target using amplitudes
              and phase probability distribution
    residual: standard crystallographic residual
      vector: vector residual
       mixed: (1-fom)*residual + fom*vector
        e2e2: correlation coefficient using normalized E^2
        e1e1: correlation coefficient using normalized E
        f2f2: correlation coefficient using F^2
        f1f1: correlation coefficient using F +}
{+ choice: "mlf" "mli" "mlhl" "residual" "vector" "mixed"
           "e2e2" "e1e1" "f2f2" "f1f1" +}
{===>} reftarget="mlf";

{* number of bins for refinement target *}
{* this will be determined automatically if a negative value is given
   otherwise the specified number of bins will be used *}
{===>} target_bins=-1;

{* memory allocation for FFT calculation *}
{* this will be determined automatically if a negative value is given
   otherwise the specified number of words will be allocated *}
{===>} fft_memory=-1;

{=========================== output files ============================}

{* output listing file *}
{===>} list_outfile="optimize_rweight.list";

{===========================================================================}
{         things below this line do not normally need to be changed         }
{===========================================================================}

 ) {- end block parameter definition -}

 checkversion 1.3

 evaluate ($log_level=quiet)

 if ( $log_level = verbose ) then
   set message=normal echo=on end
 else
   set message=off echo=off end
 end if

 if ( &BLANK%structure_infile = true ) then
 
    {- read topology files -}
    topology
     evaluate ($counter=1)
     evaluate ($done=false)
     while ( $done = false ) loop read
      if ( &exist_topology_infile_$counter = true ) then
         if ( &BLANK%topology_infile_$counter = false ) then
            @@&topology_infile_$counter
         end if
      else
        evaluate ($done=true)
      end if
      evaluate ($counter=$counter+1)
     end loop read
    end
    
    @CNS_XTALMODULE:mtfautogenerate (
                                  coordinate_infile=&coordinate_infile;
                                  convert=true;
                                  separate=true;
                                  atom_delete=(not known);
                                  hydrogen_flag=true;
                                  break_cutoff=2.5;
                                  disulphide_dist=3.0;
                                  carbo_dist=2.5;
                                  patch_infile=&patch_infile;
                                  O5_becomes="O";
                                 )

 else

   structure @&structure_infile end
   coordinates @&coordinate_infile

 end if

 {- read parameter files -}
 parameter
  evaluate ($counter=1)
  evaluate ($done=false)
  while ( $done = false ) loop read
   if ( &exist_parameter_infile_$counter = true ) then
      if ( &BLANK%parameter_infile_$counter = false ) then
         @@&parameter_infile_$counter
      end if
   else
     evaluate ($done=true)
   end if
   evaluate ($counter=$counter+1)
  end loop read
 end

 set message=normal echo=on end

 xray

   @CNS_XTALLIB:spacegroup.lib (sg=&sg;)

   a=&a b=&b c=&c  alpha=&alpha beta=&beta gamma=&gamma

   @CNS_XRAYLIB:scatter.lib

   evaluate ($counter=1)
   evaluate ($done=false)
   while ( $done = false ) loop read
    if ( &exist_reflection_infile_$counter = true ) then
      if ( &BLANK%reflection_infile_$counter = false ) then
       reflection
         @@&reflection_infile_$counter
       end
      end if
   else
     evaluate ($done=true)
   end if
   evaluate ($counter=$counter+1)
  end loop read

 end

 if ( &BLANK%anom_library = false ) then
   @@&anom_library
 else
   set echo=off end
   xray anomalous=? end
   if ( $result = true ) then
     display Warning: no anomalous library has been specified
     display          no anomalous contribution will used in refinement
   end if
   set echo=on end
 end if

 {- copy define parameters of optional arrays into symbols so 
    we can redefine them -}
    
 evaluate ($obs_i=&obs_i)
 evaluate ($obs_sigi=&obs_sigi)
 evaluate ($obs_w=&obs_w)
 xray
   @@CNS_XTALMODULE:checkrefinput (
                                  reftarget=&reftarget;
                                  obs_f=&obs_f;
                                  obs_sigf=&obs_sigf;
                                  test_set=&test_set;
                                  obs_pa=&obs_pa;
                                  obs_pb=&obs_pb;
                                  obs_pc=&obs_pc;
                                  obs_pd=&obs_pd;
                                  obs_phase=&obs_phase;
                                  obs_fom=&obs_fom;
                                  obs_w=$obs_w;
                                  obs_i=$obs_i;
                                  obs_sigi=$obs_sigi;
                                  )

   query name=fcalc domain=reciprocal end
   if ( $object_exist = false ) then
      declare name=fcalc domain=reciprocal type=complex end
   end if
   declare name=fbulk domain=reciprocal type=complex end
   do (fbulk=0) ( all )

   binresolution &low_res &high_res
   mapresolution &high_res

   if ( &obs_type = "intensity" ) then
     if ( &BLANK%obs_i = true ) then
       display  Error: observed intensity array is undefined
       display         aborting script
       abort
     end if
     evaluate ($reject_obs=&obs_i)
     evaluate ($reject_sig=&obs_sigi)
   else
     evaluate ($reject_obs=&obs_f)
     evaluate ($reject_sig=&obs_sigf)
   end if

   declare name=ref_active domain=reciprocal type=integer end
   declare name=tst_active domain=reciprocal type=integer end

   do (ref_active=0) ( all )
   do (ref_active=1) ( ( $STRIP%reject_sig # 0 ) and
                      ( &low_res >= d >= &high_res ) )

   statistics overall
     completeness
     selection=( ref_active=1 )
   end
   evaluate ($total_compl=$expression1)

   show sum(1) ( ref_active=1 )
   evaluate ($total_read=$select)
   evaluate ($total_theor=int(1./$total_compl * $total_read))

   show rms (amplitude($STRIP%reject_obs)) ( ref_active=1 )
   evaluate ($obs_high=$result*&obs_rms)
   show min (amplitude($STRIP%reject_obs)) ( ref_active=1 )
   evaluate ($obs_low=$result)

   do (ref_active=0) ( all )
   do (ref_active=1)
                  ( ( amplitude($STRIP%reject_obs) > &sigma_cut*$STRIP%reject_sig ) and
                    ( $STRIP%reject_sig # 0 ) and
                    ( $obs_low <= amplitude($STRIP%reject_obs) <= $obs_high ) and
                    ( &low_res >= d >= &high_res ) )

   do (tst_active=0) (all)
   do (tst_active=1) (ref_active=1 and &STRIP%test_set=&test_flag)

   show sum(1) ( ref_active=1 and tst_active=0 )
   evaluate ($total_work=$select)
   show sum(1) ( ref_active=1 and tst_active=1 )
   evaluate ($total_test=$select)
   evaluate ($total_used=$total_work+$total_test)

   evaluate ($unobserved=$total_theor-$total_read)
   evaluate ($rejected=$total_read-$total_used)
   evaluate ($per_unobs=100*($unobserved/$total_theor))
   evaluate ($per_reject=100*($rejected/$total_theor))
   evaluate ($per_used=100*($total_used/$total_theor))
   evaluate ($per_work=100*($total_work/$total_theor))
   evaluate ($per_test=100*($total_test/$total_theor))

   associate fcalc ( &atom_select )

   tselection=( ref_active=1 )

   cvselection=( tst_active=1 )

   method=FFT          
   
 {- MODIFIED 2/15/06 -}
 end
 

 show min ( b ) ( &atom_select )
 evaluate ($b_min=$result)
 @@CNS_XTALMODULE:fft_parameter_check ( 
                             d_min=&high_res; 
                             b_min=$b_min;
                             grid=auto;
                             fft_memory=&fft_memory;
                             fft_grid=$fft_grid;   
                             fft_b_add=$fft_b_add; 
                             fft_elim=$fft_elim; 
                                      )
                            
 xray
 {- END MODIFICATION -}

   tolerance=0.0 lookup=false

 end                  

 xray
   @@CNS_XTALMODULE:checkcv (active=ref_active;
                             test=tst_active;)
 end

 fix selection=(not(&atom_select) or &atom_fixed) end

 igroup interaction (&atom_select) (&atom_select) end
 
 flags exclude * include xref end

 evaluate ($best_test_r=1)

 if ( &BLANK%ncs_infile = false ) then
    inline @&ncs_infile
 end if

 if ( &reset_b > 0 ) then
    do (b=&reset_b) (&atom_select)
 end if

 xray
   predict
     mode=reciprocal
     to=fcalc
     selection=(ref_active=1)
     atomselection=( &atom_select ) 
   end
 end

 {- BEGIN MODIFICATION -}
 @CNS_XTALMODULE:scale_and_solvent_grid_search (
                             bscale=&bscale;
                             sel=( ref_active=1 );
                             sel_test=( tst_active=1 );
                             atom_select=( &atom_select );
                             bulk_sol=&bulk_sol;
                             bulk_mask=&bulk_mask_infile;
                             bulk_atoms=( &atom_select );
                             
                             sol_auto=&sol_auto;
                             sol_k=&sol_k;
                             sol_b=&sol_b;
                             sol_rad=&sol_rad;
                             sol_shrink=&sol_shrink;
 
                             fcalc=fcalc;
                             obs_f=&STRIP%obs_f;
                             obs_sigf=&STRIP%obs_sigf;
                             obs_i=$STRIP%obs_i;
                             obs_sigi=$STRIP%obs_sigi;                             
                             fpart=fbulk;
                             
!
! Begin modification (6/28/06)                             
                             Baniso_11=$Baniso_11;
                             Baniso_22=$Baniso_22;
                             Baniso_33=$Baniso_33;
                             Baniso_12=$Baniso_12;
                             Baniso_13=$Baniso_13;
                             Baniso_23=$Baniso_23;
                             Biso=$Biso_model;
! End modification
! 
                             
                             sol_k_best=$sol_k_ref;
                             sol_b_best=$sol_b_ref;
			     solrad_best=$solrad_best;
			     shrink_best=$shrink_best;
                             
                             b=b;

                             low_b_flag=$low_b_flag;
                            
                             sol_output=&sol_output;
                             
                             )
 xray
   @@CNS_XTALMODULE:calculate_r (
                                 fobs=&STRIP%obs_f;
                                 fcalc=fcalc;
                                 fpart=fbulk;
                                 sel=( ref_active=1 );
                                 sel_test=( tst_active=1 );
                                 print=true;
                                 output=OUTPUT;
                                 r=$start_r;
                                 test_r=$start_test_r;)
 end

 {- check the gridding again since the minimum B-factor may have changed -}
 show min ( b ) ( &atom_select )
 evaluate ($b_min=$result)
 @@CNS_XTALMODULE:fft_parameter_check ( 
                             d_min=&high_res; 
                             b_min=$b_min;
                             grid=auto;
                             fft_memory=&fft_memory;
                             fft_grid=$fft_grid;   
                             fft_b_add=$fft_b_add; 
                             fft_elim=$fft_elim; 
                                      )
 {- END MODIFICATION -}

 xray
    @@CNS_XTALMODULE:calculate_r (fobs=&STRIP%obs_f;
                                 fcalc=fcalc;
                                 fpart=fbulk;
                                 sel=(ref_active=1);
                                 sel_test=(tst_active=1);
                                 print=true;
                                 output=OUTPUT;
                                 r=$start_r;
                                 test_r=$start_test_r;)
 end

 xray
   @@CNS_XTALMODULE:refinementtarget (target=&reftarget;
                                     sig_sigacv=0.07;
                                     mbins=&target_bins;
                                     fobs=&STRIP%obs_f;
                                     sigma=&STRIP%obs_sigf;
                                     weight=$STRIP%obs_w;
                                     iobs=$STRIP%obs_i;
                                     sigi=$STRIP%obs_sigi;
                                     test=tst_active;
                                     fcalc=fcalc;
                                     fpart=fbulk;
                                     pa=&STRIP%obs_pa;
                                     pb=&STRIP%obs_pb;
                                     pc=&STRIP%obs_pc;
                                     pd=&STRIP%obs_pd;
                                     phase=&STRIP%obs_phase;
                                     fom=&STRIP%obs_fom;
                                     sel=(ref_active=1);
                                     sel_test=(tst_active=1);
                                     statistics=true;)
 end

 @@CNS_XTALMODULE:one_term_wa (wa=$wa;)

 set display=&list_outfile end

 display >>> refinement resolution: &low_res - &high_res A  
 display >>> starting r= $start_r[f6.4] free_r= $start_test_r[f6.4]
 display >>> wa= $wa  target= &STRIP%reftarget
 display >>> sg= &STRIP%sg a= &a b= &b c= &c alpha= &alpha beta= &beta gamma= &gamma

 evaluate ($counter=1)
 evaluate ($done=false)
 while ( $done = false ) loop read
  if ( &exist_parameter_infile_$counter = true ) then
    if ( &BLANK%parameter_infile_$counter = false ) then
      display >>> parameter file $counter  : &STRIP%parameter_infile_$counter
    end if
  else
   evaluate ($done=true)
  end if
  evaluate ($counter=$counter+1)
 end loop read
 
 if ( &BLANK%structure_infile = true ) then
   display >>> molecular structure file: automatic

   evaluate ($counter=1)
   evaluate ($done=false)
   while ( $done = false ) loop read
    if ( &exist_topology_infile_$counter = true ) then
      if ( &BLANK%topology_infile_$counter = false ) then
        display >>> topology file $counter  : &STRIP%topology_infile_$counter
      end if
    else
     evaluate ($done=true)
    end if
    evaluate ($counter=$counter+1)
   end loop read

   evaluate ($counter=1)
   evaluate ($done=false)
   while ( $done = false ) loop read
    if ( &exist_link_infile_$counter = true ) then
      if ( &BLANK%link_infile_$counter = false ) then
        display >>> linkage file $counter  : &STRIP%link_infile_$counter
      end if
    else
     evaluate ($done=true)
    end if
    evaluate ($counter=$counter+1)
   end loop read

   if ( &BLANK%patch_infile = false ) then
      display >>> custom patch file = &STRIP%patch_infile
   end if

 else
   display >>> molecular structure file: &STRIP%structure_infile
 end if

 display >>> input coordinates: &STRIP%coordinate_infile
 if ( &BLANK%anom_library = false ) then
   display >>> anomalous f' f'' library: &STRIP%anom_library
 end if

 evaluate ($counter=1)
 evaluate ($done=false)
 while ( $done = false ) loop read
    if ( &exist_reflection_infile_$counter = true ) then
      if ( &BLANK%reflection_infile_$counter = false ) then
         display >>> reflection file $counter : &STRIP%reflection_infile_$counter       
      end if
   else
     evaluate ($done=true)
   end if
   evaluate ($counter=$counter+1)
 end loop read
 
 if ( &BLANK%ncs_infile = false ) then
   display >>> ncs= &STRIP%ncs_type  ncs file= &STRIP%ncs_infile
 else
   display >>> ncs= none
 end if
 if ( &bscale # "no" ) then
   if ( $low_b_flag = true ) then
     display >>> warning: B-correction gave atomic B-values less than zero
     display >>>          they have been reset to zero
   end if
 end if
 ! 
 ! Begin modification (6/28/06)
 if ( &bscale = "anisotropic" ) then
   display >>> Anisotropic B-factor tensor Ucart of atomic model without isotropic component :
   display >>>   B11=$Baniso_11[f8.3] B22=$Baniso_22[f8.3] B33=$Baniso_33[f8.3]
   display >>>   B12=$Baniso_12[f8.3] B13=$Baniso_13[f8.3] B23=$Baniso_23[f8.3]
   display >>> Isotropic component added to coordinate array B: $Biso_model[f8.3]
 elseif ( &bscale = "isotropic" ) then
   display >>> B-factor applied to coordinate array B: $Biso_model[f8.3]
 else
   display >>> initial B-factor correction: none
 end if
 ! End modification
 !

 {- MODIFIED 5/18/05 -}
 if ( &bulk_sol = true ) then 
     display >>> bulk solvent: probe radius=$solrad_best, shrink value=$solrad_best
     display >>> bulk solvent: density level= $sol_k_ref e/A^3, B-factor= $sol_b_ref A^2
 else
     display >>> bulk solvent: false
 end if
 {- END MODIFICATION -}
 
 if ( &obs_type = "intensity" ) then
   display >>> reflections with Iobs/sigma_I < &sigma_cut rejected
   display >>> reflections with Iobs > &obs_rms * rms(Iobs) rejected
 else
   display >>> reflections with |Fobs|/sigma_F < &sigma_cut rejected
   display >>> reflections with |Fobs| > &obs_rms * rms(Fobs) rejected
 end if
 xray anomalous=? end
 if ( $result = true ) then
   display >>> anomalous diffraction data was input
 end if
 
 {- MODIFIED 2/15/06 -}
 display >>> fft gridding factor = $fft_grid, B factor offset = $fft_b_add A^2, Elimit = $fft_elim
 {- END MODIFICATION -}
 
 display >>> theoretical total number of refl. in resol. range:    $total_theor[I6] ( 100.0 % )
 display >>> number of unobserved reflections (no entry):          $unobserved[I6] ( $per_unobs[f5.1] % )
 display >>> number of reflections rejected:                       $rejected[I6] ( $per_reject[f5.1] % )
 display >>> total number of reflections used:                     $total_used[I6] ( $per_used[f5.1] % )
 display >>> number of reflections in working set:                 $total_work[I6] ( $per_work[f5.1] % )
 display >>> number of reflections in test set:                    $total_test[I6] ( $per_test[f5.1] % )

 set display=OUTPUT end

 if (&rweight < 0) then
   @@CNS_XTALMODULE:get_rweight (selected=&atom_select;
                                 fixed=&atom_fixed;
                                 rweight=$rweight_current;)
 else
   evaluate ($rweight_current=&rweight)
 end if

 xray
   optimize bfactors

     method=lbfgs

     bmin=&bmin
     bmax=&bmax

     nstep=0
     drop=10.0

     bsigma=( (&atom_select and not(&atom_fixed)) and &atom_main )=&bsig_main
     bsigma=( (&atom_select and not(&atom_fixed)) and not(&atom_main) )=&bsig_side

     asigma=( (&atom_select and not(&atom_fixed)) and &atom_main )=&asig_main
     asigma=( (&atom_select and not(&atom_fixed)) and not(&atom_main) )=&asig_side

     rweight=$rweight_current
   end
 end

 evaluate ($rweight_init=$b_rweight)

 set display=&list_outfile end

 display
 display ------> initial B rmsd for bonded mainchain atoms= $brms_bond_1[f8.3]  target= &bsig_main
 display ------> initial B rmsd for bonded sidechain atoms= $brms_bond_2[f8.3]  target= &bsig_side
 display ------> initial B rmsd for angle mainchain atoms= $brms_angl_1[f8.3]  target= &asig_main
 display ------> initial B rmsd for angle sidechain atoms= $brms_angl_2[f8.3]  target= &asig_side
 display
 display ------> initial rweight estimate= $rweight_init[f8.4]
 display 

 set display=OUTPUT end

 do (store9=b) (all)

 for $scale in ( 0.025 0.05 0.1 0.2 0.5 1 2 5 10 20 50 ) loop main

   do (b=store9) (all)

   xray
      predict
        mode=reciprocal
        to=fcalc
        selection=(ref_active=1)
        atomselection=( &atom_select ) 
      end
   end

   xray
     @@CNS_XTALMODULE:refinementtarget (target=&reftarget;
                                       sig_sigacv=0.07;
                                       mbins=&target_bins;
                                       fobs=&STRIP%obs_f;
                                       sigma=&STRIP%obs_sigf;
                                       weight=$STRIP%obs_w;
                                       iobs=$STRIP%obs_i;
                                       sigi=$STRIP%obs_sigi;
                                       test=tst_active;
                                       fcalc=fcalc;
                                       fpart=fbulk;
                                       pa=&STRIP%obs_pa;
                                       pb=&STRIP%obs_pb;
                                       pc=&STRIP%obs_pc;
                                       pd=&STRIP%obs_pd;
                                       phase=&STRIP%obs_phase;
                                       fom=&STRIP%obs_fom;
                                       sel=(ref_active=1);
                                       sel_test=(tst_active=1);
                                       statistics=true;)
   end

   evaluate ($rweight_current=$rweight_init*$scale)

   xray
     optimize bfactors

       method=lbfgs

       bmin=&bmin
       bmax=&bmax

       nstep=&bfactor_nstep
       drop=10.0

       bsigma=( (&atom_select and not(&atom_fixed)) and &atom_main )=&bsig_main
       bsigma=( (&atom_select and not(&atom_fixed)) and not(&atom_main) )=&bsig_side

       asigma=( (&atom_select and not(&atom_fixed)) and &atom_main )=&asig_main
       asigma=( (&atom_select and not(&atom_fixed)) and not(&atom_main) )=&asig_side

       rweight=$rweight_current
     end
   end

   xray
      predict
        mode=reciprocal
        to=fcalc
        selection=(ref_active=1)
        atomselection=( &atom_select ) 
      end
      @@CNS_XTALMODULE:calculate_r (fobs=&STRIP%obs_f;
                                   fcalc=fcalc;
                                   fpart=fbulk;
                                   sel=(ref_active=1);
                                   sel_test=(tst_active=1);
                                   print=true;
                                   output=OUTPUT;
                                   r=$full_r;
                                   test_r=$full_test_r;)
   end
  
   set display=&list_outfile end

   display rweight= $rweight_current[f8.4] r= $full_r[f6.4] free_r= $full_test_r[f6.4] rms B(bond)= $brms_bond[f8.4] rms B(angle)= $brms_angl[f8.4]

   set display=OUTPUT end

   if ( $full_test_r <= $best_test_r ) then
     evaluate ($best_test_r=$full_test_r)
     evaluate ($best_rweight=$rweight_current)
   end if

 end loop main

 set display=&list_outfile end

 display
 display ------> lowest free_r for target &reftarget with rweight= $best_rweight[f8.4] (with wa= $wa)
 display
 
 stop