CMAP testing

Jana — Fri, 19 Feb 2010 15:28:01 GMT

Current revision posted to Computational Chemistry and Biophysics Wiki by Jana on 2/19/2010 9:28:01 AM

CMAP testing

Test the performance of new CHARMM torsion potential for GBSW implicit-solvent simulations

New CMAP (par_mod24_2_6.prm): recently optimized by the Feig group at MSU to correct for the helical bias vs extended regions

par31_2_6: same CMAP as above but with the new force field for alkanes from the MacKerell group at UMBT

par31feigmp2_d1: CMAP optimized based on the MP2 map version 1

GBSW CMAP (par_all22_prot_gbsw.inp): an analytic function was added to the old CMAP to correct for the helical bias for GBSW implicit-solvent simulations. GBSW CMAP was able to fold both helical and beta-sheet proteins (Chen et al, JACS 2006)

par31feigmp2_d2: CMAP optimized based on the MP2 map version 2

Old CMAP (par_all22_prot_cmap.inp): Phi, Psi grid map to correction for overstabilization of pi helix
(Feig et al, JPCB 2003, MacKerell et al, JCC 2004, MacKerell et al, JACS 2004)

Ala dipeptide

20 ns REX-GBSW simulations, data collected in the last 5 ns at 298 K

mp2_d1

mp2_d2

Comparison to explicit-solvent results: PPII is not enough deep or AlpaR is not enough high.

GBMV

Similar

Even more helical

GBMV

Less helical

expt GBSW GBMV

3JHNHa: 5.68 5.09 5.67

expt GBSW GBMV

3JHNHa: 5.68 5.20 5.64

Ala3 (free N-ter and protonated C-ter)

20 ns REX-GBSW simulations, data collected in the last 5 ns at 298 K.

par31feigmp2_d1 residue #2

par31_2_6 residue #2

AlphaR is too stable.

Similar to Ala dipep map. Alpha-L is too high as compared to explicit-solvent data (consistent with the ala-dipep map).

Time averaged NMR coupling
simulation expt

3JHNHa 4.93                        5.68
3JHNCp                                1.13
3JHACp                                1.84
3JCpCp                              0.25
3JHNCb                              2.39
1JNCa    11.04                  11.34
2JNCa      7.92                    8.45

Much better agreement with experiment!

Time averaged NMR coupling
simulation

3JHNHa 5.00

1JNCa 1.19

2JNCa 8.18

Ala5

20 ns REX-GBSW simulations, data collected in the last 5 ns at 295 K

mp2_d1 res 2	mp2_d1 res 2 (GBMV)
Same problem as in Ala dipep.	.Alpha-R region is less stable than in GBSW.
mp2_d1 res 3	mp2_d1 res 3 (GBMV)
AlphaR region is slightly more stabilized.	AlphaR region is less stable than GBSW
mp2_d1 res 4	mp2_d1 res 4 (GBMV)
AlphaR region is as stable as PPII region. Helicity is building up as the peptide lengths increases. This has to do with overstabilization of hydrogen bonding in GB.	AlpahaR region is less stable than GBSW.
J-coup res 2 expt res 3 expt res 4 expt 3JHNHa 4.97 5.59 4.98 5.74 5.13 5.98	J-coup res 2 expt res 3 expt res 4 expt 3JHNHa 5.27 5.59 5.24 5.74 5.37 5.98 GBMV gives better agreement with expt

mp2_d1  res 2

mp2_d1 res 2 (GBMV)

Same problem as in Ala dipep.

.Alpha-R region is less stable than in GBSW.

mp2_d1
res 3
mp2_d1 res 3 (GBMV)

AlphaR region is slightly more stabilized.

AlphaR region is less stable than GBSW

mp2_d1  res 4

mp2_d1  res 4 (GBMV)

AlphaR region is as stable as PPII region. Helicity is building up as the peptide lengths increases. This has to do with overstabilization of hydrogen bonding in GB.

AlpahaR region is less stable than GBSW.

J-coup      res 2 expt   res 3 expt   res 4 expt

3JHNHa   4.97   5.59  4.98   5.74 5.13    5.98

J-coup      res 2  expt res 3  expt res 4 expt

3JHNHa    5.27   5.59 5.24   5.74  5.37 5.98

GBMV gives better agreement with expt

mp2_d2  res 2

mp2_d2 res 2 (GBMV)

mp2_d2 res 3

mp2_d2 res 3 (GBMV)

mp2_d2  res 4

mp2_d2  res 4 (GBMV)

AlphaR region is as stable as PPII region. Helicity is building up as the peptide lengths increases. This has to do with overstabilization of hydrogen bonding in GB.

J-coup      res 2 expt   res 3 expt   res 4 expt

3JHNHa   5.05   5.59  5.25   5.74 5.33    5.98

J-coup      res 2  expt res 3  expt res 4 expt

3JHNHa    5.27   5.59 5.24   5.74  5.37 5.98

GBMV gives better agreement with expt

(AAQAA)3

30 ns REX-GBSW simulations, data collected in the last 5 ns at 275 (red) and 300 K (green). Convergence verified by evaluating 30-40 ns data and compare it with 25-30 ns.

New CMAP (helicity based on hydrogen bonding)

Old CMAP (helicity based on hydrogen bonding)

Residue-averaged helix content is comparable to experiment although helicity for residues in the middle is significantly higher. We will investigate the backbone hydrogen bonding.

GBSW CMAP

Good agreement because the backbone atomic radii were optimized to match the experimental data.

HP36 fragments (test influence from side chains):

helicity assigned by DSSP

HP13 (N-terminal 13 residues)

With the new CMAP, overall helicity is significantly reduced. NMR J coupling data suggests sparsely populated helical states. We will compare with J coupling data.

C-terminal 14 residues

New CMAP (red) gave much lower helicity in agreement with experiment. We need to compare with NMR data which suggests low helicity.

Middle 10 residues

This is an exception: new CMAP (red) gives slightly higher helicity for residues in the middle of the sequence. NMR data suggests no helicity.

CMAP testing

Jana — Fri, 19 Feb 2010 15:18:11 GMT

Revision 54 posted to Computational Chemistry and Biophysics Wiki by Jana on 2/19/2010 9:18:11 AM

CMAP testing

Test the performance of new CHARMM torsion potential for GBSW implicit-solvent simulations

New CMAP (par_mod24_2_6.prm): recently optimized by the Feig group at MSU to correct for the helical bias vs extended regions

par31_2_6: same CMAP as above but with the new force field for alkanes from the MacKerell group at UMBT

par31feigmp2_d1: CMAP optimized based on thequantum MP2 map version 1

par31feigmp2_d2: CMAP optimized based on the MP2 map version 2

Old CMAP (par_all22_prot_cmap.inp): Phi, Psi grid map to correction for overstabilization of pi helix
(Feig et al, JPCB 2003, MacKerell et al, JCC 2004, MacKerell et al, JACS 2004)

Ala dipeptide

20 ns REX-GBSW simulations, data collected in the last 5 ns at 298 K

par31feigmp2_d1

par31_2_6

mp2_d1

mp2_d2

Comparison to explicit-solvent results: Diff(AlphaR, PPII) is too small by 1 kcal/mol. PPII is not enough deep or AlpaR is not enough high.

GBMV

Compare to GBSW: alpha-L region more stable

Similar

Even more helical

GBMV(stilll to come...)

Very similar to the GBSW map.

J-coupling data

Less helical

expt GBSW GBMV

3JHNHa: 5.68

time average 5.09 5.66

from PMF 3.95 4.39
chi-square 5.04 4.98

J-coupling data 5.67

expt GBSW GBMV

3JHNHa: 5.68

time average 5.09 5.61

from PMF 3.26 3.76
chi-square 9.20 7.48 5.20 5.64

Ala3 (free N-ter and protonated C-ter)

20 ns REX-GBSW simulations, data collected in the last 5 ns at 298 K.

par31feigmp2_d1 residue #2

par31_2_6 residue #2

AlphaR is too stable.

Similar to Ala dipep map. Alpha-L is too high as compared to explicit-solvent data (consistent with the ala-dipep map).

Time averaged NMR coupling
simulation expt

Time averaged NMR coupling
simulation

3JHNHa 5.00

1JNCa 1.19

2JNCa 8.18

Ala5

20 ns REX-GBSW simulations, data collected in the last 5 ns at 295 K

par31feigmp2_d1

mp2_d1 res 2	par31feigmp2_d1	mp2_d1 res 2 (GBMV)
Same problem as in Ala dipep.	.Alpha-R region is less stable than in GBSW.
par31feigmp2_d1
mp2_d1 res 3	par31feigmp2_d1	mp2_d1 res 3 (GBMV)
AlphaR region is slightly more stabilized.	AlphaR region is less stable than GBSW
par31feigmp2_d1
mp2_d1 res 4	par31feigmp2_d1	mp2_d1 res 4 (GBMV)
AlphaR region is as stable as PPII region. Helicity is building up as the peptide lengths increases. This has to do with overstabilization of hydrogen bonding in GB.	AlpahaR region is less stable than GBSW.
J-coup res 2 expt res 3 expt res 4 expt 3JHNHa 4.97 5.59 4.98 5.74 5.13 5.98 3JHNCp 3JHACp 3JCpCp 3JHNCb 1JNCa 2JNCa	J-coup res 2 expt res 3 expt res 4 expt 3JHNHa 5.27 5.59 5.24 5.74 5.37 5.98 GBMV gives better agreement with expt

(AAQAA)3

30 ns REX-GBSW simulations, data collected in the last 5 ns at 275 (red) and 300 K (green). Convergence verified by evaluating 30-40 ns data and compare it with 25-30 ns.

New CMAP (helicity based on hydrogen bonding)

Old CMAP (helicity based on hydrogen bonding)

Residue-averaged helix content is comparable to experiment although helicity for residues in the middle is significantly higher. We will investigate the backbone hydrogen bonding.

GBSW CMAP

Good agreement because the backbone atomic radii were optimized to match the experimental data.

HP36 fragments (test influence from side chains):

helicity assigned by DSSP

HP13 (N-terminal 13 residues)

With the new CMAP, overall helicity is significantly reduced. NMR J coupling data suggests sparsely populated helical states. We will compare with J coupling data.

C-terminal 14 residues

New CMAP (red) gave much lower helicity in agreement with experiment. We need to compare with NMR data which suggests low helicity.

Middle 10 residues

This is an exception: new CMAP (red) gives slightly higher helicity for residues in the middle of the sequence. NMR data suggests no helicity.

CMAP testing

Jana — Thu, 18 Feb 2010 14:59:23 GMT

Revision 53 posted to Computational Chemistry and Biophysics Wiki by Jana on 2/18/2010 8:59:23 AM

CMAP testing

Test the performance of new CHARMM torsion potential for GBSW implicit-solvent simulations

New CMAP (par_mod24_2_6.prm): recently optimized by the Feig group at MSU to correct for the helical bias vs extended regions

par31_2_6: same CMAP as above but with the new force field for alkanes from the MacKerell group at UMBT

par31feigmp2_d1: CMAP optimized based on the quantum map

Old CMAP (par_all22_prot_cmap.inp): Phi, Psi grid map to correction for overstabilization of pi helix
(Feig et al, JPCB 2003, MacKerell et al, JCC 2004, MacKerell et al, JACS 2004)

Ala dipeptide

20 ns REX-GBSW simulations, data collected in the last 5 ns at 298 K

par31feigmp2_d1

par31_2_6

Comparison to explicit-solvent results: Diff(AlphaR, PPII) is too small by 1 kcal/mol. PPII is not enough deep or AlpaR is not enough high.

GBMV

Compare to GBSW: alpha-L region more stable

Comparison

More helical

GBMV (stilll to explicit-solvent results: Diff(AlphaR, PPIIcome...)too small by 1 kcal/mol. Diff(AlphaL,PPII): too small by 0.5 kcal/mol

GBMV

Very similar to the GBSW map.

J-coupling data

expt GBSW GBMV
3JHNHa: 5.68

time average 5.09 5.66

from PMF 3.95 4.39
chi-square 5.04 4.98

J-coupling data

expt GBSW GBMV
3JHNHa: 5.68

time average 5.09 5.61

from PMF 3.26 3.76
chi-square 9.20 7.48

Ala3 (free N-ter and protonated C-ter)

20 ns REX-GBSW simulations, data collected in the last 5 ns at 298 K.

par31feigmp2_d1 residue #2

par31_2_6 residue #2

AlphaR is too stable.

Similar to Ala dipep map. Alpha-L is too high as compared to explicit-solvent data (consistent with the ala-dipep map).

Time averaged NMR coupling
simulation expt

Time averaged NMR coupling
simulation

3JHNHa 5.00

1JNCa 1.19

2JNCa 8.18

Ala5

20 ns REX-GBSW simulations, data collected in the last 5 ns at 295 K

par31feigmp2_d1 res 2	par31feigmp2_d1 res 2 (GBMV)
Same problem as in Ala dipep.	.Alpha-R region is less stable than in GBSW.
par31feigmp2_d1 res 3	par31feigmp2_d1 res 3 (GBMV)
AlphaR region is slightly more stabilized.	AlphaR region is less stable than GBSW
par31feigmp2_d1 res 4	par31feigmp2_d1 res 4 (GBMV)
AlphaR region is as stable as PPII region. Helicity is building up as the peptide lengths increases. This has to do with overstabilization of hydrogen bonding in GB.	AlpahaR region is less stable than GBSW.
J-coup res 2 expt res 3 expt res 4 expt 3JHNHa 4.97 5.59 4.98 5.74 5.13 5.98 3JHNCp 3JHACp 3JCpCp 3JHNCb 1JNCa 2JNCa	J-coup res 2 expt res 3 expt res 4 expt 3JHNHa 5.27 5.59 5.24 5.74 5.37 5.98 GBMV gives better agreement with expt

(AAQAA)3

30 ns REX-GBSW simulations, data collected in the last 5 ns at 275 (red) and 300 K (green). Convergence verified by evaluating 30-40 ns data and compare it with 25-30 ns.

New CMAP (helicity based on hydrogen bonding)

Old CMAP (helicity based on hydrogen bonding)

Residue-averaged helix content is comparable to experiment although helicity for residues in the middle is significantly higher. We will investigate the backbone hydrogen bonding.

GBSW CMAP

Good agreement because the backbone atomic radii were optimized to match the experimental data.

HP36 fragments (test influence from side chains):

helicity assigned by DSSP

HP13 (N-terminal 13 residues)

With the new CMAP, overall helicity is significantly reduced. NMR J coupling data suggests sparsely populated helical states. We will compare with J coupling data.

C-terminal 14 residues

New CMAP (red) gave much lower helicity in agreement with experiment. We need to compare with NMR data which suggests low helicity.

Middle 10 residues

This is an exception: new CMAP (red) gives slightly higher helicity for residues in the middle of the sequence. NMR data suggests no helicity.

CMAP testing

Jana — Tue, 16 Feb 2010 14:56:44 GMT

Revision 52 posted to Computational Chemistry and Biophysics Wiki by Jana on 2/16/2010 8:56:44 AM

CMAP testing

Test the performance of new CHARMM torsion potential for GBSW implicit-solvent simulations

New CMAP (par_mod24_2_6.prm): recently optimized by the Feig group at MSU to correct for the helical bias vs extended regions

par31_2_6: same CMAP as above but with the new force field for alkanes from the MacKerell group at UMBT

par31feigmp2_d1: CMAP optimized based on the quantum map

Old CMAP (par_all22_prot_cmap.inp): Phi, Psi grid map to correction for overstabilization of pi helix
(Feig et al, JPCB 2003, MacKerell et al, JCC 2004, MacKerell et al, JACS 2004)

Ala dipeptide

20 ns REX-GBSW simulations, data collected in the last 5 ns at 298 K

par31feigmp2_d1

par31_2_6

Comparison to explicit-solvent results: Diff(AlphaR, PPII) is too small by 1 kcal/mol. PPII is not enough deep or AlpaR is not enough high.

GBMV

Compare to GBSW: alpha-L region more stable

Comparison to explicit-solvent results: Diff(AlphaR, PPII) too small by 1 kcal/mol. Diff(AlphaL,PPII): too small by 0.5 kcal/mol

GBMV

Very similar to the GBSW map.

J-coupling data

expt GBSW GBMV
3JHNHa: 5.68

time average 5.09 5.66

from PMF 3.95 4.39
chi-square 5.04 4.98

J-coupling data

expt GBSW GBMV
3JHNHa: 5.68

time average 5.09 5.61

from PMF 3.26 3.76
chi-square 9.20 7.48

Ala3 (free N-ter and protonated C-ter)

20 ns REX-GBSW simulations, data collected in the last 5 ns at 298 K.

par22_2_6

par31feigmp2_d1 residue #2	par31_2_6 residue #2
Same as Ala dipeptide, the PPII region
AlphaR is more too stableby 0.5 kcal/mol.	Similar to Ala dipep map. Alpha-L is too high as compared to explicit-solvent data (consistent with the ala-dipep map).
Ensemble
Time averaged NMR coupling simulation expt 3JHNHa 5.074219 4.93 5.68 3JHNCp1.376013 1.13 3JHACp1.728351 1.84 3JCpCp 0.503688 0.25 3JHNCb2.141917 2.39 1JNCa 11.256388 11.04 11.34 2JNCa 8.264948 7.92 8.45 Much better agreement with experiment!	Ensemble	Time averaged NMR coupling simulation 3JHNHa 5.00 1JNCa 1.19 2JNCa 8.18

Ala5

20 ns REX-GBSW simulations, data collected in the last 5 ns at 295 K

par31feigmp2_d1 res 2	par31feigmp2_d1 res 2 (GBMV)
Same problem as in Ala dipep.	.Alpha-R region is less stable than in GBSW.
par31feigmp2_d1 res 3	par31feigmp2_d1 res 3 (GBMV)
AlphaR region is slightly more stabilized.	AlphaR region is less stable than GBSW
par31feigmp2_d1 res 4	par31feigmp2_d1 res 4 (GBMV)
AlphaR region is as stable as PPII region. Helicity is building up as the peptide lengths increases. This has to do with overstabilization of hydrogen bonding in GB.	AlpahaR region is less stable than GBSW.
J-coup res 2 expt res 3 expt res 4 expt 3JHNHa 4.97 5.59 4.98 5.74 5.13 5.98 3JHNCp 3JHACp 3JCpCp 3JHNCb 1JNCa 2JNCa	J-coup res 2 expt res 3 expt res 4 expt 3JHNHa 5.27 5.59 5.24 5.74 5.37 5.98 GBMV gives better agreement with expt

(AAQAA)3

30 ns REX-GBSW simulations, data collected in the last 5 ns at 275 (red) and 300 K (green). Convergence verified by evaluating 30-40 ns data and compare it with 25-30 ns.

New CMAP (helicity based on hydrogen bonding)

Old CMAP (helicity based on hydrogen bonding)

Residue-averaged helix content is comparable to experiment although helicity for residues in the middle is significantly higher. We will investigate the backbone hydrogen bonding.

GBSW CMAP

Good agreement because the backbone atomic radii were optimized to match the experimental data.

HP36 fragments (test influence from side chains):

helicity assigned by DSSP

HP13 (N-terminal 13 residues)

With the new CMAP, overall helicity is significantly reduced. NMR J coupling data suggests sparsely populated helical states. We will compare with J coupling data.

C-terminal 14 residues

New CMAP (red) gave much lower helicity in agreement with experiment. We need to compare with NMR data which suggests low helicity.

Middle 10 residues

This is an exception: new CMAP (red) gives slightly higher helicity for residues in the middle of the sequence. NMR data suggests no helicity.

CMAP testing

Jana — Tue, 16 Feb 2010 03:24:24 GMT

Revision 51 posted to Computational Chemistry and Biophysics Wiki by Jana on 2/15/2010 9:24:24 PM

CMAP testing

Test the performance of new CHARMM torsion potential for GBSW implicit-solvent simulations

New CMAP (par_mod24_2_6.prm): recently optimized by the Feig group at MSU to correct for the helical bias vs extended regions

par31_2_6: same CMAP as above but with the new force field for alkanes from the MacKerell group at UMBT

par31feigmp2_d1: CMAP optimized based on the quantum map

Old CMAP (par_all22_prot_cmap.inp): Phi, Psi grid map to correction for overstabilization of pi helix
(Feig et al, JPCB 2003, MacKerell et al, JCC 2004, MacKerell et al, JACS 2004)

Ala dipeptide

20 ns REX-GBSW simulations, data collected in the last 5 ns at 298 K

par31feigmp2_d1

par31_2_6

Comparison to explicit-solvent results: Diff(AlphaR, PPII) is too small by 1 kcal/mol. PPII is not enough deep or AlpaR is not enough high.

GBMV

Compare to GBSW: alpha-L region more stable

Comparison to explicit-solvent results: Diff(AlphaR, PPII) too small by 1 kcal/mol. Diff(AlphaL,PPII): too small by 0.5 kcal/mol

GBMV

Very similar to the GBSW map.

J-coupling data

expt GBSW GBMV
3JHNHa: 5.68

time average 5.09 5.66

from PMF 3.95 4.39
chi-square 5.04 4.98

J-coupling data

expt GBSW GBMV
3JHNHa: 5.68

time average 5.09 5.61

from PMF 3.26 3.76
chi-square 9.20 7.48

Ala3 (free N-ter and protonated C-ter)

20 ns REX-GBSW simulations, data collected in the last 5 ns at 298 K.

par22_2_6 residue #2

par31_2_6 residue #2

Same as Ala dipeptide, the PPII region is more stable by 0.5 kcal/mol.

Similar to Ala dipep map. Alpha-L is too high as compared to explicit-solvent data (consistent with the ala-dipep map).

Ensemble averaged NMR coupling
simulation expt

3JHNHa 5.074219                5.68
3JHNCp 1.376013                1.13
3JHACp 1.728351                1.84
3JCpCp 0.503688                0.25
3JHNCb 2.141917                2.39
1JNCa   11.256388              11.34
2JNCa   8.264948                 8.45

Much better agreement with experiment!

Ensemble averaged NMR coupling
simulation

Ala5

20 ns REX-GBSW simulations, data collected in the last 5 ns at 295 K

par31feigmp2_d1 res 2	par31feigmp2_d1 res 2 (GBMV)
Same problem as in Ala dipep.	.Alpha-R region is less stable than in GBSW.
par31feigmp2_d1 res 3	par31feigmp2_d1 res 3 (GBMV)
AlphaR region is slightly more stabilized.	AlphaR region is less stable than GBSW
par31feigmp2_d1 res 4	par31feigmp2_d1 res 4 (GBMV)
AlphaR region is as stable as PPII region. Helicity is building up as the peptide lengths increases. This has to do with overstabilization of hydrogen bonding in GB.	AlpahaR region is less stable than GBSW.
J-coup res 2 expt res 3 expt res 4 expt 3JHNHa 4.97 5.59 4.98 5.74 5.13 5.98 3JHNCp 3JHACp 3JCpCp 3JHNCb 1JNCa 2JNCa	J-coup res 2 expt res 3 expt res 4 expt 3JHNHa 5.27 5.59 5.24 5.74 5.37 5.98 GBMV gives better agreement with expt

(AAQAA)3

30 ns REX-GBSW simulations, data collected in the last 5 ns at 275 (red) and 300 K (green). Convergence verified by evaluating 30-40 ns data and compare it with 25-30 ns.

New CMAP (helicity based on hydrogen bonding)

Old CMAP (helicity based on hydrogen bonding)

Residue-averaged helix content is comparable to experiment although helicity for residues in the middle is significantly higher. We will investigate the backbone hydrogen bonding.

GBSW CMAP

Good agreement because the backbone atomic radii were optimized to match the experimental data.

HP36 fragments (test influence from side chains):

helicity assigned by DSSP

HP13 (N-terminal 13 residues)

With the new CMAP, overall helicity is significantly reduced. NMR J coupling data suggests sparsely populated helical states. We will compare with J coupling data.

C-terminal 14 residues

New CMAP (red) gave much lower helicity in agreement with experiment. We need to compare with NMR data which suggests low helicity.

Middle 10 residues

This is an exception: new CMAP (red) gives slightly higher helicity for residues in the middle of the sequence. NMR data suggests no helicity.

mp2_d2 res 2	mp2_d2 res 2 (GBMV)

mp2_d2 res 3	mp2_d2 res 3 (GBMV)

mp2_d2 res 4	mp2_d2 res 4 (GBMV)
AlphaR region is as stable as PPII region. Helicity is building up as the peptide lengths increases. This has to do with overstabilization of hydrogen bonding in GB.
J-coup res 2 expt res 3 expt res 4 expt 3JHNHa 5.05 5.59 5.25 5.74 5.33 5.98	J-coup res 2 expt res 3 expt res 4 expt 3JHNHa 5.27 5.59 5.24 5.74 5.37 5.98 GBMV gives better agreement with expt