Merge pull request #2 from freeenergylab/dev

dev to main for release

abfe/abfe_alchemy_md.py

@@ -502,13 +502,26 @@ def _add_boresch_restraint(args, prmtop, lig_masks, rec_masks, lig_idx, rst_refs
             temperature = args.temperature
             kr = args.bond_const
             ktheta = args.angle_const
+            kalpha = args.angle_const
             kphi = args.dihedral_const
+            kbeta = args.dihedral_const
+            kgamma = args.dihedral_const
             rst_correction = analytic.restraint_correction(
-                T=temperature, r0=r0, theta0=theta0, kr=kr, ktheta=ktheta, kphi=kphi
+                T=temperature, r0=r0, theta0=theta0,
+                kr=kr, ktheta=ktheta, kalpha=kalpha, kphi=kphi, kbeta=kbeta, kgamma=kgamma
                 )
             results = np.array([[rst_correction]]).T
             df = pd.DataFrame(results, columns=['Total (kcal/mol)'])
             df.to_csv('results.csv', float_format='%.2f')
+            # Just dump out the correction results from schrodinger for comparison.
+            _rst_correction = analytic.restraint_correction_schrodinger(
+                T=temperature, r0=r0, alpha0=alpha0, theta0=theta0,
+                gamma0=gamma0, beta0=beta0, phi0=phi0,
+                Kr=args.bond_const, Kang=args.angle_const, Kdihed=args.dihedral_const
+                )
+            _results = np.array([[_rst_correction]]).T
+            _df = pd.DataFrame(_results, columns=['Total (kcal/mol)'])
+            _df.to_csv('results_schrodinger.csv', float_format='%.2f')
         #==========================================================================
         # 2.2 VDW
         #==========================================================================

abfe/md/analytic.py

@@ -12,7 +12,7 @@
 """
 from math import pi, log, sin, sqrt, exp, erf
 
-def restraint_correction(T, r0, theta0, kr, ktheta, kphi):
+def restraint_correction(T, r0, theta0, kr, ktheta, kalpha, kphi, kbeta, kgamma):
     """Do Boresch-style restraint analytic correction, refer to
 
     Calculation of Standard Binding Free Energies: Aromatic Molecules
@@ -29,7 +29,10 @@ def restraint_correction(T, r0, theta0, kr, ktheta, kphi):
         theta0 (float): equilibrium value for angle theta
         kr (float): force constant for distance r
         ktheta (float): force constant for angle theta
+        kalpha (float): force constant for angle alpha
         kphi (float): force constant for dihedral phi
+        kbeta (float): force constant for dihedral beta
+        kgamma (float): force constant for dihedral gamma
  
     Returns:
         FtC0 + Fr (float): Boresch analytic restraint correction value
@@ -39,13 +42,16 @@ def restraint_correction(T, r0, theta0, kr, ktheta, kphi):
     theta0 = float(theta0)
     kr     = float(kr)*2.0
     ktheta = float(ktheta)*2.0
+    kalpha = float(kalpha)*2.0
     kphi   = float(kphi)*2.0
+    kbeta   = float(kbeta)*2.0
+    kgamma   = float(kgamma)*2.0
 
     V = 1660. # in A^3
     kB = 0.0019872041 # Boltzmann's constant (kcal/mol/K)
     FtC0 = -(kB*T)*log(r0**2*sin(theta0/180.0*pi)\
         *sqrt((2*pi*kB*T)**3/(kr*ktheta*kphi))/V) # Eq. 38
-    Fr = -(kB*T)*log(1.0/(8*pi**2)*(2*pi*kB*T/kr)**1.5) # Eq. 40
+    Fr = -(kB*T)*log(1.0/(8*pi**2)*sqrt((2*pi*kB*T)**3/(kalpha*kbeta*kgamma))) # Eq. 40
     print('Translational: %.2f kcal/mol' % FtC0)
     print('Rotational: %.2f kcal/mol' % Fr)
 
@@ -108,6 +114,13 @@ def restraint_correction_schrodinger(T, r0, alpha0, theta0, gamma0, beta0, phi0,
     """Just do test for restraint_correction function.
     """
     correction = restraint_correction(
-        T=298.15, ktheta=100., theta0=85.370, kphi=100., kr=10., r0=7.230,
+        T=298.15, r0=4.470, theta0=101.230,
+        kr=10, ktheta=100, kalpha=100, kphi=100, kbeta=100, kgamma=100
         )
-    print('The reference value is 8.99 kcal/mol, while this calculated value is %.2f kcal/mol.' % correction)
+    print('The reference value is 11.62 kcal/mol, while this calculated restraint_correction is %.2f kcal/mol.' % correction)
+    correction = restraint_correction_schrodinger(
+        T=298.15, r0=4.470, alpha0=72.140, theta0=101.230,
+        gamma0=77.887, beta0=-137.094, phi0=9.048,
+        Kr=10, Kang=100, Kdihed=100
+        )
+    print('The reference value is 11.65 kcal/mol, while this calculated restraint_correction_schrodinger is %.2f kcal/mol.' % correction)

testing/abfe_testing/dG_components_results.csv

@@ -1,4 +1,3 @@
 ,MBAR_dG_solvated_vdw,MBAR_dG_solvated_cc,TI_dG_solvated_vdw,TI_dG_solvated_cc,MBAR_dG_complex_vdw,MBAR_dG_complex_cc,MBAR_dG_complex_restraint,MBAR_dG_analytic,TI_dG_complex_vdw,TI_dG_complex_cc,TI_dG_complex_restraint,TI_dG_analytic
-bnz,1.06,0.00,1.04,0.00,7.92,0.00,-6.11,9.57,7.75,0.00,-6.71,9.57
-,MBAR_dG_solvated_vdw,MBAR_dG_solvated_cc,TI_dG_solvated_vdw,TI_dG_solvated_cc,MBAR_dG_complex_vdw,MBAR_dG_complex_cc,MBAR_dG_complex_restraint,MBAR_dG_analytic,TI_dG_complex_vdw,TI_dG_complex_cc,TI_dG_complex_restraint,TI_dG_analytic
-phn,5.18,0.00,5.12,0.00,9.66,0.00,-6.06,9.61,9.74,0.00,-6.27,9.61
+phn,5.18,0.00,5.12,0.00,9.66,0.00,-6.06,11.63,9.74,0.00,-6.27,11.63
+bnz,1.06,0.00,1.04,0.00,7.92,0.00,-6.11,11.64,7.75,0.00,-6.71,11.64

testing/abfe_testing/dG_results.csv

@@ -1,4 +1,3 @@
 ,MBAR_dG,MBAR_dG_std,TI_dG,TI_dG_std
-bnz,-3.40,0.08,-3.85,0.10
-,MBAR_dG,MBAR_dG_std,TI_dG,TI_dG_std
-phn,-0.94,0.10,-1.28,0.10
+phn,1.08,0.10,0.74,0.10
+bnz,-1.33,0.08,-1.78,0.10