* This is pymerk v0.1.0 * Starting workflow with 10 conformers ************************* * Stage: 1_prescreening * ************************* * Filtering on g* (threshold: 0.006374 a.u.) * Setup Summary: - Components: elec=MAIN, gsolv=AUX, gtrv=NONE - Main driver: OrcaDriver[pbe d3/def2-SV(P)] - Aux driver: XtbDriver[gfn2,gbsa(thf)] > Conformer #1: -1927.36999830 a.u. > Conformer #2: -1927.36910273 a.u. > Conformer #3: -1927.36856281 a.u. > Conformer #4: -1927.36679383 a.u. > Conformer #5: -1927.36785651 a.u. > Conformer #6: -1927.37048317 a.u. > Conformer #7: -1927.37139197 a.u. > Conformer #8: -1927.37100522 a.u. > Conformer #9: -1927.36852492 a.u. > Conformer #10: -1927.36304327 a.u. * Final values: g* Δg* Conformer #1 -1927.36999830 0.00139367 * Conformer #2 -1927.36910273 0.00228924 * Conformer #3 -1927.36856281 0.00282916 * Conformer #4 -1927.36679383 0.00459813 * Conformer #5 -1927.36785651 0.00353546 * Conformer #6 -1927.37048317 0.00090880 * Conformer #7 -1927.37139197 0.00000000 * Conformer #8 -1927.37100522 0.00038675 * Conformer #9 -1927.36852492 0.00286705 * Conformer #10 -1927.36304327 0.00834870 * Done, retained 9 conformer(s) * RMSD matrix (Å) for 9 structures: ..r #1 ..r #2 ..r #3 ..r #4 ..r #5 ..r #6 ..r #7 ..r #8 ..r #9 Conformer #1 0.000 Conformer #2 0.596 0.000 Conformer #3 1.094 1.233 0.000 Conformer #4 1.330 1.183 0.618 0.000 Conformer #5 1.360 1.474 0.349 0.643 0.000 Conformer #6 1.732 1.830 2.067 2.190 2.210 0.000 Conformer #7 1.649 1.751 1.996 2.125 2.143 0.599 0.000 Conformer #8 1.759 1.657 2.081 2.038 2.216 0.862 0.613 0.000 Conformer #9 1.720 1.820 2.093 2.220 2.241 0.205 0.655 0.925 0.000 ********************** * Stage: 2_screening * ********************** * Filtering on G* (threshold: 0.005578 a.u.) * Setup Summary: - Components: elec=MAIN, gsolv=MAIN, gtrv=AUX - Main driver: OrcaDriver[r2scan-3c/def2-mTZVPP,smd(tetrahydrofuran)] - Aux driver: XtbDriver[gfn2,gbsa(thf)] > Conformer #1: -1928.72998373 a.u. > Conformer #2: -1928.72917797 a.u. > Conformer #3: -1928.72837593 a.u. > Conformer #4: -1928.72697880 a.u. > Conformer #5: -1928.72713514 a.u. > Conformer #6: -1928.73043307 a.u. > Conformer #7: -1928.73048205 a.u. > Conformer #8: -1928.73021348 a.u. > Conformer #9: -1928.72915363 a.u. * Final values: G* ΔG* Conformer #1 -1928.72998373 0.00049832 * Conformer #2 -1928.72917797 0.00130408 * Conformer #3 -1928.72837593 0.00210612 * Conformer #4 -1928.72697880 0.00350325 * Conformer #5 -1928.72713514 0.00334691 * Conformer #6 -1928.73043307 0.00004898 * Conformer #7 -1928.73048205 0.00000000 * Conformer #8 -1928.73021348 0.00026857 * Conformer #9 -1928.72915363 0.00132842 * * Done, retained 9 conformer(s) * RMSD matrix (Å) for 9 structures: ..r #1 ..r #2 ..r #3 ..r #4 ..r #5 ..r #6 ..r #7 ..r #8 ..r #9 Conformer #1 0.000 Conformer #2 0.596 0.000 Conformer #3 1.094 1.233 0.000 Conformer #4 1.330 1.183 0.618 0.000 Conformer #5 1.360 1.474 0.349 0.643 0.000 Conformer #6 1.732 1.830 2.067 2.190 2.210 0.000 Conformer #7 1.649 1.751 1.996 2.125 2.143 0.599 0.000 Conformer #8 1.759 1.657 2.081 2.038 2.216 0.862 0.613 0.000 Conformer #9 1.720 1.820 2.093 2.220 2.241 0.205 0.655 0.925 0.000 ********************* * Stage: 3_optimize * ********************* * Macro-Optimization on G* (threshold: 0.004781 a.u.) * Setup Summary: - Components: elec=MAIN, gsolv=MAIN, gtrv=AUX - Main driver: OrcaDriver[r2scan-3c/def2-mTZVPP,smd(tetrahydrofuran)] - Aux driver: XtbDriver[gfn2,gbsa(thf)] > Macrocycle 1 - Otimizing Conformer #1... E=-1928.77302771, grad=0.016784 [NOT CONVERGED] - Otimizing Conformer #2... E=-1928.77295768, grad=0.016667 [NOT CONVERGED] - Otimizing Conformer #3... E=-1928.77330021, grad=0.018177 [NOT CONVERGED] - Otimizing Conformer #4... E=-1928.77301709, grad=0.017722 [NOT CONVERGED] - Otimizing Conformer #5... E=-1928.77229602, grad=0.017388 [NOT CONVERGED] - Otimizing Conformer #6... E=-1928.77361177, grad=0.017566 [NOT CONVERGED] - Otimizing Conformer #7... E=-1928.77349481, grad=0.017240 [NOT CONVERGED] - Otimizing Conformer #8... E=-1928.77303233, grad=0.017279 [NOT CONVERGED] - Otimizing Conformer #9... E=-1928.77382920, grad=0.017675 [NOT CONVERGED] → retained 9 conformer(s) > Macrocycle 2 - Otimizing Conformer #1... E=-1928.77914650, grad=0.010644 [NOT CONVERGED] - Otimizing Conformer #2... E=-1928.77919673, grad=0.010655 [NOT CONVERGED] - Otimizing Conformer #3... E=-1928.77999569, grad=0.011913 [NOT CONVERGED] - Otimizing Conformer #4... E=-1928.77953865, grad=0.010643 [NOT CONVERGED] - Otimizing Conformer #5... E=-1928.77937474, grad=0.015141 [NOT CONVERGED] - Otimizing Conformer #6... E=-1928.77954065, grad=0.011201 [NOT CONVERGED] - Otimizing Conformer #7... E=-1928.77967820, grad=0.011955 [NOT CONVERGED] - Otimizing Conformer #8... E=-1928.77917046, grad=0.013855 [NOT CONVERGED] - Otimizing Conformer #9... E=-1928.77916968, grad=0.009322 [NOT CONVERGED] → retained 9 conformer(s) > Macrocycle 3 - Otimizing Conformer #1... E=-1928.78151517, grad=0.010718 [NOT CONVERGED] - Otimizing Conformer #2... E=-1928.78133010, grad=0.010217 [NOT CONVERGED] - Otimizing Conformer #3... E=-1928.78188768, grad=0.012678 [NOT CONVERGED] - Otimizing Conformer #4... E=-1928.78161302, grad=0.010248 [NOT CONVERGED] - Otimizing Conformer #5... E=-1928.78257420, grad=0.011785 [NOT CONVERGED] - Otimizing Conformer #6... E=-1928.78220200, grad=0.011244 [NOT CONVERGED] - Otimizing Conformer #7... E=-1928.78249045, grad=0.011445 [NOT CONVERGED] - Otimizing Conformer #8... E=-1928.78235279, grad=0.012536 [NOT CONVERGED] - Otimizing Conformer #9... E=-1928.78129662, grad=0.010044 [NOT CONVERGED] → retained 9 conformer(s) > Macrocycle 4 - Otimizing Conformer #1... E=-1928.78490641, grad=0.018756 [NOT CONVERGED] - Otimizing Conformer #2... E=-1928.78381092, grad=0.012692 [NOT CONVERGED] - Otimizing Conformer #3... E=-1928.78627929, grad=0.012779 [NOT CONVERGED] - Otimizing Conformer #4... E=-1928.78578860, grad=0.020505 [NOT CONVERGED] - Otimizing Conformer #5... E=-1928.78839902, grad=0.018355 [NOT CONVERGED] - Otimizing Conformer #6... E=-1928.78597848, grad=0.017054 [NOT CONVERGED] - Otimizing Conformer #7... E=-1928.78661962, grad=0.016879 [NOT CONVERGED] - Otimizing Conformer #8... E=-1928.78652716, grad=0.015147 [NOT CONVERGED] - Otimizing Conformer #9... E=-1928.78458063, grad=0.012629 [NOT CONVERGED] → retained 9 conformer(s) > Macrocycle 5 - Otimizing Conformer #1... E=-1928.79369502, grad=0.012539 [NOT CONVERGED] - Otimizing Conformer #2... E=-1928.79460004, grad=0.029011 [NOT CONVERGED] - Otimizing Conformer #3... E=-1928.79406931, grad=0.012735 [NOT CONVERGED] - Otimizing Conformer #4... E=-1928.79495595, grad=0.012822 [NOT CONVERGED] - Otimizing Conformer #5... E=-1928.79560609, grad=0.008616 [NOT CONVERGED] - Otimizing Conformer #6... E=-1928.79260713, grad=0.011855 [NOT CONVERGED] - Otimizing Conformer #7... E=-1928.79171977, grad=0.006051 [NOT CONVERGED] - Otimizing Conformer #8... E=-1928.79254052, grad=0.025737 [NOT CONVERGED] - Otimizing Conformer #9... E=-1928.79014324, grad=0.007283 [NOT CONVERGED] → retained 8 conformer(s) > Macrocycle 6 - Otimizing Conformer #1... E=-1928.79632813, grad=0.009871 [NOT CONVERGED] - Otimizing Conformer #2... E=-1928.79706226, grad=0.008321 [NOT CONVERGED] - Otimizing Conformer #3... E=-1928.79554638, grad=0.005453 [NOT CONVERGED] - Otimizing Conformer #4... E=-1928.79498081, grad=0.003733 [NOT CONVERGED] - Otimizing Conformer #5... E=-1928.79596289, grad=0.005593 [NOT CONVERGED] - Otimizing Conformer #6... E=-1928.79477773, grad=0.007267 [NOT CONVERGED] - Otimizing Conformer #7... E=-1928.79423398, grad=0.006896 [NOT CONVERGED] - Otimizing Conformer #8... E=-1928.79573457, grad=0.007073 [NOT CONVERGED] → retained 8 conformer(s) > Macrocycle 7 - Otimizing Conformer #1... E=-1928.79837042, grad=0.006560 [NOT CONVERGED] - Otimizing Conformer #2... E=-1928.79715134, grad=0.008322 [CONVERGED] - Otimizing Conformer #3... E=-1928.79564309, grad=0.005453 [CONVERGED] - Otimizing Conformer #4... E=-1928.79437346, grad=0.003732 [CONVERGED] - Otimizing Conformer #5... E=-1928.79602255, grad=0.005598 [CONVERGED] - Otimizing Conformer #6... E=-1928.79770014, grad=0.010852 [NOT CONVERGED] - Otimizing Conformer #7... E=-1928.79681750, grad=0.013492 [NOT CONVERGED] - Otimizing Conformer #8... E=-1928.79886170, grad=0.010926 [NOT CONVERGED] → retained 8 conformer(s) > Macrocycle 8 - Otimizing Conformer #1... E=-1928.79841420, grad=0.006561 [CONVERGED] - Otimizing Conformer #6... E=-1928.80003175, grad=0.006218 [NOT CONVERGED] - Otimizing Conformer #7... E=-1928.80041361, grad=0.005542 [NOT CONVERGED] - Otimizing Conformer #8... E=-1928.80071451, grad=0.005523 [NOT CONVERGED] → retained 6 conformer(s) > Macrocycle 9 - Otimizing Conformer #6... E=-1928.80123923, grad=0.004664 [NOT CONVERGED] - Otimizing Conformer #7... E=-1928.80048334, grad=0.005540 [CONVERGED] - Otimizing Conformer #8... E=-1928.80147675, grad=0.006496 [NOT CONVERGED] → retained 5 conformer(s) > Macrocycle 10 - Otimizing Conformer #6... E=-1928.80133117, grad=0.004664 [CONVERGED] - Otimizing Conformer #8... E=-1928.80136756, grad=0.003163 [NOT CONVERGED] → retained 5 conformer(s) > Macrocycle 11 - Otimizing Conformer #8... E=-1928.80139099, grad=0.003163 [CONVERGED] → retained 5 conformer(s) * Final values: G* ΔG* Conformer #1 -1928.79841420 0.00297679 * Conformer #2 -1928.79715134 0.00423965 * Conformer #3 -1928.79564309 0.00574790 Conformer #4 -1928.79437346 0.00701754 Conformer #5 -1928.79602255 0.00536844 Conformer #6 -1928.80133117 0.00005982 * Conformer #7 -1928.80048334 0.00090765 * Conformer #8 -1928.80139099 0.00000000 * Conformer #9 -1928.79014324 0.01124775 * Done, retained 5 conformer(s) * RMSD matrix (Å) for 5 structures: ..r #1 ..r #2 ..r #6 ..r #7 ..r #8 Conformer #1 0.000 Conformer #2 0.589 0.000 Conformer #6 1.733 1.842 0.000 Conformer #7 1.692 1.805 0.584 0.000 Conformer #8 1.808 1.740 0.871 0.650 0.000 *********************** * Stage: 4_refinement * *********************** * Boltzmann population filtering on ΔG* (threshold: 0.950) * Setup Summary: - Components: elec=MAIN, gsolv=MAIN, gtrv=AUX - Main driver: OrcaDriver[wb97x-d3/def2-TZVPP,smd(tetrahydrofuran)] - Aux driver: XtbDriver[gfn2,gbsa(thf)] > Conformer #1: -1929.08595168 a.u. > Conformer #2: -1929.08479631 a.u. > Conformer #6: -1929.08917852 a.u. > Conformer #7: -1929.08823314 a.u. > Conformer #8: -1929.08901520 a.u. * Final Boltzmann population: G* ΔG* Pop % Conformer #1 -1929.08595168 0.00322684 1.5 Conformer #2 -1929.08479631 0.00438221 0.4 Conformer #6 -1929.08917852 0.00000000 44.4 * Conformer #7 -1929.08823314 0.00094538 16.3 * Conformer #8 -1929.08901520 0.00016332 37.4 * * Done, retained 3 conformer(s)