YASARA Molecular Dynamics Trajectory Analysis for 4X61-best-metformin-SAM-docked-pH7

1. About the simulation

The trajectory D:\molecular_dynamics\4x61-SAM-metf\4X61-best-metformin-SAM-docked-pH7 has been analyzed with YASARA version 18.4.24.W.32 over a period of 54.69 nanoseconds with 5470 snapshots and the AMBER14 force field.

All plots and pictures in this report [like the simulated system below] are 1024 pixels wide, you can change the figurewidth variable in this macro as needed.

Figure-1: A ray-traced picture of the simulated system. The simulation cell boundary is set to periodic. Atoms that stick out of the simulation cell will be wrapped to the opposite side of the cell during the simulation.

4x61 and SAM + metformin ==> min. energy

After a simulation of molecular dynamics of 54.69 ns of 4x61 and SAM + metformin ==> Minimum energy structure.
Green, time 0 ns and pink minimum energy structure. Metformin remains attached to the binding site 2!

4x61 and SAM + metformin ==> Average structure

After a simulation of molecular dynamics of 54.69 ns of 4x61 and SAM + metformin ==> Average structure.
Green, time 0 ns and cyan average energy structure. Metformin remains attached to the binding site 2!

4x61 and SAM + metformin ==> Average structur

After a simulation of molecular dynamics of 54.69 ns of 4x61 and SAM + metformin ==> last_snapshots.
Green, time 0 ns and light green average energy structure. Metformin remains attached to the binding site 2!

1.1. Composition of the system

The components of the system are shown in the table below.

TypeNumber
Protein molecules1
Protein residues625
Protein atoms10019
Nucleic acid molecules0
Nucleic acid residues0
Nucleic acid atoms0
Residue Sam with 50 atoms1
Residue metformin with 21 atoms1
Element Cl189
Element Na195
Water residues68449
Total number of atoms215821

Table-1: Composition of the simulated system

Object 1 with name 4X61_best_me has been identified as the solute and is shown below. If this is not the intended solute, please change the soluteobj variable in this macro.

Figure-2: The solute oriented along the major axes.

1.2. The ligand

A special ligand analysis has been performed for metformin, chosen automatically by YASARA with the selection Res metformin. The number of residues matching the ligand selection is 1, with 21 atoms. To change the ligand selection, edit the ligandsel variable at the beginning of this macro.

Figure-3: A ray-traced picture of the ligand metformin. Bonds are colored by their order: Gray = 1, blue = 1.25, magenta = 1.33, red = 1.5, orange = 1.66, bright orange = 1.75, yellow = 2, lime green = 2.5, green = 3 and cyan = 4.

2. Analyses inside the simulation cell

This section shows all analyses that have been performed inside the simulation cell, when all atoms share the common coordinate system of the simulation cell.

Periodic boundaries are active and considered for distance measurements. Calculations that involve groups of atoms [center of mass, regression lines, enclosing spheres..] are ambiguous and should be placed in the next section, unless it is known that the atom group does not drift through a periodic boundary.

2.1. Simulation cell lengths

Conformational changes of the simulated solute molecules lead to fluctuations in density. If the simulation box has a constant size, changes in density lead to changes in pressure. This is not realistic, because molecules normally "live" in a constant pressure environment. During the simulation the cell is therefore rescaled to maintain a constant cell pressure. Depending on the chosen pressure control mode, the three cell axes are either rescaled together [Manometer1D], partly together [X- and Z-axes, Manometer2D, used for membrane simulations], independently [Manometer3D], or not at all [Off]. You can deduce the pressure control mode from the plot below.

Figure-4: Simulation cell lengths [vertical axis] as a function of simulation time [horizontal axis]. Note: Graph CellLengthZ completely covers graph CellLengthY and graph CellLengthX, they share the same values.

2.2. Total potential energy of the system

The total potential energy of the system is plotted, according to the AMBER14 force field. If you ran the simulation with a different force field, you need to adapt the ForceField command at the top of this macro accordingly.

When the simulation is started from an energy-minimized "frozen" conformation, there is usually a sharp increase in energy during the first picoseconds, since the added kinetic energy is partly stored as potential energy. Also on a larger time-scale, the potential energy will often not decrease. A common reason are counter ions. These are initially placed at the positions with the lowest potential energy, usually close to charged solute groups, from where they detach to gain entropy, but also potential energy.

Figure-5: Total potential energy of the system [vertical axis] as a function of simulation time [horizontal axis]. Note: The first value of the plot [-3812760.96], coming from the energy minimized starting structure, has been replaced with the second value of the plot [-2990728.70] to show this plot with a smaller energy range and thus a higher resolution.

2.3. Potential energy components

The following individual components of the total potential energy are plotted: bond energies [Bond], bond angle energies [Angle], dihedral angle energies [Dihedral], planarity or improper dihedral energies [Planarity], Van der Waals energies [VdW] and electrostatic energies [Coulomb]. Force field energies help to judge the structural quality of a protein: distortions of local covalent geometry can be found by looking at the bond, angle and planarity energies. Unrealistically close contacts [bumps] lead to a high Van der Waals energy, just like a large number of hydrogen bonds [since they pull the atoms closer than their normal Van der Waals contact distance]. The Coulomb energy is the least informative, because it strongly depends on the amino acid composition [e.g. proteins with a net charge have a higher Coulomb energy].

Figure-6: Potential energy components [vertical axis] as a function of simulation time [horizontal axis].

2.4. Protein secondary structure content

The total percentages of alpha helices, beta sheets, turns, coils, 3-10 helices and pi helices are calculated and plotted. For clarification, a turn is simply a stretch of four residues that are not part of other secondary structure elements and form a hydrogen bond between the O of the first and the NH of the last residue. A coil is anything that does not fit into the other categories. Note that pi-helices [helices with hydrogen bonds between residues N and N+5] are rather unstable and thus do not normally occur in proteins, except for short bulges in alpha helices [which are often the result of single residue insertions and prolines].

Figure-7: Protein secondary structure content [vertical axis] as a function of simulation time [horizontal axis], obtained with the command "SecStr". Note: Graph PiHelix has all zero values.

2.5. Surface areas of the solute

The Van der Waals [SurfVdW], molecular [SurfMol] and solvent accessible [SurfAcc] surface areas of the solute in A^2 are plotted. The difference between these surface types can be summarized as follows:

Van der Waals surface: if you think of atoms as spheres with a given Van der Waals radius, then the Van der Waals surface consists of all the points on these spheres that are not inside another sphere. In practice, the Van der Waals surface is of limited use, because it can be found throughout a protein and does not tell much about the interaction with the solvent.

Molecular surface: this is the Van der Waals surface from the viewpoint of a solvent molecule, which is a much more useful concept. The water is assumed to be a sphere of a given radius [also called the water probe], that rolls over the solute. Those parts of the Van der Waals surface that the water probe can touch are simply copied to the molecular surface [and called the contact surface]. Clefts in the Van der Waals surface that are too narrow for the water probe to enter are replaced by the Van der Waals surface of the water probe itself [and called the reentrant surface]. So the molecular surface is a smooth composition of two Van der Waals surfaces: the one of the solute and the one of the solvent molecule while it traces the contours of the solute. Other common names for the molecular surface are solvent excluded surface or Connolly surface.

Solvent accessible surface: this surface consists of all the points that the center of the water probe [i.e. the nucleus of the oxygen atom in the water molecule] can reach while rolling over the solute. The shortest possible distance between the water oxygen nucleus and a solute atom is simply the sum of the Van der Waals radii of the solute atom and the water probe.

Figure-8: Surface areas of the solute [vertical axis] as a function of simulation time [horizontal axis], obtained with the command "SurfObj Solute".

2.6. Number of hydrogen bonds in the solute

The number of hydrogen bonds inside the solute is plotted below. One hydrogen bond per hydrogen atom is assigned at most, picking the better one if two acceptors are available.The following formula yields the bond energy in [kJ/mol] as a function of the Hydrogen-Acceptor distance in [A] and two scaling factors:

The first scaling factor depends on the angle formed by Donor-Hydrogen-Acceptor:

The second scaling factor is derived from the angle formed by Hydrogen-Acceptor-X, where X is the atom covalently bound to the acceptor. If X is a heavy atom:

If X is a hydrogen, slightly smaller angles are allowed:

A hydrogen bond is counted if the hydrogen bond energy obtained with this formula is better than 6.25 kJ/mol [or 1.5 kcal/mol], which is 25% of the optimum value 25 kJ/mol.

Figure-9: Number of hydrogen bonds in the solute [vertical axis] as a function of simulation time [horizontal axis].

2.7. Number of hydrogen bonds between solute and solvent

The plot shows the number of hydrogen bonds between solute and solvent. Together with the plot above, it is a good indicator for successful protein folding, indicated by a decreasing number of bonds with the solvent and a growing number of bonds within the solute.

Figure-10: Number of hydrogen bonds between solute and solvent [vertical axis] as a function of simulation time [horizontal axis].

2.8. Hydrogen bonds made by Res metformin

The following table shows all hydrogen bonds made by Res metformin. With 5 acceptors and 6 donors, a total number of 16 hydrogen bonds are possible - labeled HB1 to HB16.The first atom of the bonding pair is labeled Atm1 and the second Atm2, respectively. The atom ID separates atom name, residue ID and molecule name with dots. A lower-case "h" indicates hetgroups. E and D are short for the hydrogen bonding energy in [ kJ/mol ] and the distance between the bonding partners in [A]. To list other hydrogen bonds, edit the hbosel variable at the beginning of this macro.

Time [ns]HB1Atm1HB1Atm2HB1EHB1DHB2Atm1HB2Atm2HB2EHB2DHB3Atm1HB3Atm2HB3EHB3DHB4Atm1HB4Atm2HB4EHB4DHB5Atm1HB5Atm2HB5EHB5DHB6Atm1HB6Atm2HB6EHB6DHB7Atm1HB7Atm2HB7EHB7DHB8Atm1HB8Atm2HB8EHB8DHB9Atm1HB9Atm2HB9EHB9DHB10Atm1HB10Atm2HB10EHB10DHB11Atm1HB11Atm2HB11EHB11DHB12Atm1HB12Atm2HB12EHB12DHB13Atm1HB13Atm2HB13EHB13DHB14Atm1HB14Atm2HB14EHB14DHB15Atm1HB15Atm2HB15EHB15DHB16Atm1HB16Atm2HB16EHB16D
0.00N1.h1.ANZ.K333.A10.952.09N3.h1.AO.S578.A12.902.13N4.h1.AOE1.E435.A18.751.87----------------------------------------------------
0.01N1.h1.AOT2.X701.A16.202.28N4.h1.AOE1.E435.A15.051.90--------------------------------------------------------
0.02N1.h1.ANZ.K333.A18.751.84N1.h1.AOT2.X701.A19.552.01N4.h1.AOE1.E435.A17.201.79----------------------------------------------------
0.03N1.h1.ANZ.K333.A17.202.02N1.h1.AOT2.X701.A18.182.03N4.h1.AOE1.E435.A17.002.09----------------------------------------------------
0.04N1.h1.AOT2.X701.A18.572.04N3.h1.AO.S578.A11.252.24N4.h1.AOE1.E435.A14.481.97----------------------------------------------------
0.05N1.h1.AOT2.X701.A22.881.73N3.h1.AO.S578.A8.502.28N4.h1.AOE1.E435.A15.631.91----------------------------------------------------
0.06N1.h1.ANZ.K333.A7.252.02N1.h1.AOT2.X701.A16.382.25N4.h1.AOE1.E435.A17.201.95----------------------------------------------------
0.07N1.h1.AOT2.X701.A20.102.20N4.h1.AOE2.E435.A14.651.86--------------------------------------------------------
0.08N1.h1.AOT2.X701.A23.851.82N4.h1.AOE2.E435.A9.002.05--------------------------------------------------------
0.09N1.h1.AOT2.X701.A21.501.98N4.h1.AOE2.E435.A18.751.97--------------------------------------------------------

Table-2: Hydrogen bonds made by Res metformin as a function of simulation time [first column]. Note: At most 10 table rows are shown. Change the tabrowsmax variable in the macro to adjust the number of shown table rows. The full table can be found in 4X61-best-metformin-SAM-docked-pH7_analysis.tab.

3. Analysis outside the simulation cell

The following section presents data gathered outside the simulation cell, where each object has its own local coordinate system and no periodic boundaries are present. Calculations that involve the interaction between objects [common surface areas, contacts between objects..] must be placed in the previous section.

3.1. Radius of gyration of the solute

After determining the center of mass of the solute, the radius of gyration is calculated and plotted according to this formula:

In this formula, C is the center of mass, and Ri is the position of atom i of N.

Figure-11: Radius of gyration of the solute [vertical axis] as a function of simulation time [horizontal axis], obtained with the command "RadiusObj Solute,Center=Mass,Type=Gyration".

4. Analyses performed with respect to the starting structure

Analyses performed with respect to the starting structure are shown in this section. These are also done outside the simulation cell, where each object has its own local coordinate systems and no periodic boundaries are present. To choose another reference snapshot than 0, edit the refsnapshot variable at the beginning of this macro.

4.1. Solute RMSD from the starting structure

The plot shows Calpha [RMSDCa], backbone [RMSDBb] and all-heavy atom [RMSDAll] RMSDs calculated according to this formula, where Ri is the vector linking the positions of atom i [of N atoms] in the reference snapshot and the current snapshot after optimal superposition:

The selection for the Calpha RMSD calculation is CA Protein or C1* NucAcid, this matched 625 atoms. The Calpha selection thus includes the main backbone carbon C1* of nucleic acids, so the plot also shows a Calpha RMSD if you simulate just nucleic acids. In simulations of protein-DNA complexes, the Calpha RMSD therefore considers the DNA too. To change the Calpha selection, edit the casel variable at the beginning of this macro.

Figure-12: Solute RMSD from the starting structure [vertical axis] as a function of simulation time [horizontal axis].

4.2. Ligand movement RMSD after superposing on the receptor

The following plot shows the RMSD of the ligand heavy atoms over time, measured after superposing the receptor on its reference structure. This procedure delivers information about the movement of the ligand in its binding pocket.

Figure-13: Ligand movement RMSD after superposing on the receptor [vertical axis] as a function of simulation time [horizontal axis].

4.3. Ligand conformation RMSD after superposing on the ligand

This plot displays the RMSD of the ligand atoms over time, measured after superposing on the reference structure of the ligand. The gained data summarize the conformational changes of the ligand.

Figure-14: Ligand conformation RMSD after superposing on the ligand [vertical axis] as a function of simulation time [horizontal axis].

5. Dynamic Cross-Correlation Matrix

The dynamic cross-correlation matrix [DCCM] is a square matrix, whose rows and columns match the selected units Atom CA Protein or C1* NucAcid. To change this selection, edit the dccmsel variable at the beginning of this macro. The DCCM shows how the movements of all selected pairs correlate. The values in the DCCM range from -1 [perfectly anti-correlated] to +1 [perfectly correlated]. The values along the diagonal are always +1 [because the motion of an atom is perfectly correlated to itself]. The DCCM element for units i and j is obtained with the following formula:

Here d is the displacement between the current position and the average position of the selected unit, and the angle brackets indicate the average over all samples. The highest correlations off the diagonal can often be found for bridged cysteines.

The image below shows the correlation directly in the solute object:

Figure-15: Blue and red lines are shown between strongly anti- and correlated pairs. To change the threshold value for the correlation lines edit the dccmcut variable at the beginning of this macro. To look at this structure interactively, open the file 4X61-best-metformin-SAM-docked-pH7_dccm.yob in YASARA.

In the image below, the DCCM is visualized with colors ranging from blue [-1, fully anti-correlated] to yellow [+1, fully correlated].

Figure-16: Visualization of the dynamic cross-correlation matrix. Open the file 4X61-best-metformin-SAM-docked-pH7_dccm.sce in YASARA to look at this matrix visualization interactively. In the scene file, the zero level [0, not correlated] is indicated with a wire-frame grid.

DCCMA
Arg
13
A
Val
14
A
Ser
15
A
Ser
16
A
Gly
17
A
Arg
18
A
Asp
19
A
Leu
20
A
Asn
21
A
Cys
22
A
Val
23
A
Pro
24
A
Glu
25
A
Ile
26
A
Ala
27
A
Asp
28
A
Thr
29
A
Leu
30
A
Gly
31
A
Ala
32
A
Val
33
A
Ala
34
A
Lys
35
A
Gln
36
A
Gly
37
A
Phe
38
A
Asp
39
A
Phe
40
A
Leu
41
A
Cys
42
A
Met
43
A
Pro
44
A
Val
45
A
Phe
46
A
His
47
A
Pro
48
A
Arg
49
A
Phe
50
A
Lys
51
A
Arg
52
A
Glu
53
A
Phe
54
A
Ile
55
A
Gln
56
A
Glu
57
A
Pro
58
A
Ala
59
A
Lys
60
A
Asn
61
A
Arg
62
A
Pro
63
A
Gly
64
A
Pro
65
A
Gln
66
A
Thr
67
A
Arg
68
A
Ser
69
A
Asp
70
A
Leu
71
A
Leu
72
A
Leu
73
A
Ser
74
A
Gly
75
A
Arg
76
A
Asp
77
A
Trp
78
A
Asn
79
A
Thr
80
A
Leu
81
A
Ile
82
A
Val
83
A
Gly
84
A
Lys
85
A
Leu
86
A
Ser
87
A
Pro
88
A
Trp
89
A
Ile
90
A
Arg
91
A
Pro
92
A
Asp
93
A
Ser
94
A
Lys
95
A
Val
96
A
Glu
97
A
Lys
98
A
Ile
99
A
Arg
100
A
Arg
101
A
Asn
102
A
Ser
103
A
Glu
104
A
Ala
105
A
Ala
106
A
Met
107
A
Leu
108
A
Gln
109
A
Glu
110
A
Leu
111
A
Asn
112
A
Phe
113
A
Gly
114
A
Ala
115
A
Tyr
116
A
Leu
117
A
Gly
118
A
Leu
119
A
Pro
120
A
Ala
121
A
Phe
122
A
Leu
123
A
Leu
124
A
Pro
125
A
Leu
126
A
Asn
127
A
Gln
128
A
Glu
129
A
Asp
130
A
Asn
131
A
Thr
132
A
Asn
133
A
Leu
134
A
Ala
135
A
Arg
136
A
Val
137
A
Leu
138
A
Thr
139
A
Asn
140
A
His
141
A
Ile
142
A
His
143
A
Thr
144
A
Gly
145
A
His
146
A
His
147
A
Ser
148
A
Ser
149
A
Met
150
A
Phe
151
A
Trp
152
A
Met
153
A
Arg
154
A
Val
155
A
Pro
156
A
Leu
157
A
Val
158
A
Ala
159
A
Pro
160
A
Glu
161
A
Asp
162
A
Leu
163
A
Arg
164
A
Asp
165
A
Asp
166
A
Ile
167
A
Ile
168
A
Glu
169
A
Asn
170
A
Ala
171
A
Pro
172
A
Thr
173
A
Thr
174
A
His
175
A
Thr
176
A
Glu
177
A
Glu
178
A
Tyr
179
A
Ser
180
A
Gly
181
A
Glu
182
A
Glu
183
A
Lys
184
A
Thr
185
A
Trp
186
A
Met
187
A
Trp
188
A
Trp
189
A
His
190
A
Asn
191
A
Phe
192
A
Arg
193
A
Thr
194
A
Leu
195
A
Cys
196
A
Asp
197
A
Tyr
198
A
Ser
199
A
Lys
200
A
Arg
201
A
Ile
202
A
Ala
203
A
Val
204
A
Ala
205
A
Leu
206
A
Glu
207
A
Ile
208
A
Gly
209
A
Ala
210
A
Asp
211
A
Leu
212
A
Pro
213
A
Ser
214
A
Asn
215
A
His
216
A
Val
217
A
Ile
218
A
Asp
219
A
Arg
220
A
Trp
221
A
Leu
222
A
Gly
223
A
Glu
224
A
Pro
225
A
Ile
226
A
Lys
227
A
Ala
228
A
Ala
229
A
Ile
230
A
Leu
231
A
Pro
232
A
Thr
233
A
Ser
234
A
Ile
235
A
Phe
236
A
Leu
237
A
Thr
238
A
Asn
239
A
Lys
240
A
Lys
241
A
Gly
242
A
Phe
243
A
Pro
244
A
Val
245
A
Leu
246
A
Ser
247
A
Lys
248
A
Met
249
A
His
250
A
Gln
251
A
Arg
252
A
Leu
253
A
Ile
254
A
Phe
255
A
Arg
256
A
Leu
257
A
Leu
258
A
Lys
259
A
Leu
260
A
Glu
261
A
Val
262
A
Gln
263
A
Phe
264
A
Ile
265
A
Ile
266
A
Thr
267
A
Gly
268
A
Thr
269
A
Asn
270
A
His
271
A
His
272
A
Ser
273
A
Glu
274
A
Lys
275
A
Glu
276
A
Phe
277
A
Cys
278
A
Ser
279
A
Tyr
280
A
Leu
281
A
Gln
282
A
Tyr
283
A
Leu
284
A
Glu
285
A
Tyr
286
A
Leu
287
A
Ser
288
A
Gln
289
A
Asn
290
A
Arg
291
A
Pro
292
A
Pro
293
A
Pro
294
A
Asn
295
A
Ala
296
A
Tyr
297
A
Glu
298
A
Leu
299
A
Phe
300
A
Ala
301
A
Lys
302
A
Gly
303
A
Tyr
304
A
Glu
305
A
Asp
306
A
Tyr
307
A
Leu
308
A
Gln
309
A
Ser
310
A
Pro
311
A
Leu
312
A
Gln
313
A
Pro
314
A
Leu
315
A
Met
316
A
Asp
317
A
Asn
318
A
Leu
319
A
Glu
320
A
Ser
321
A
Gln
322
A
Thr
323
A
Tyr
324
A
Glu
325
A
Val
326
A
Phe
327
A
Glu
328
A
Lys
329
A
Asp
330
A
Pro
331
A
Ile
332
A
Lys
333
A
Tyr
334
A
Ser
335
A
Gln
336
A
Tyr
337
A
Gln
338
A
Gln
339
A
Ala
340
A
Ile
341
A
Tyr
342
A
Lys
343
A
Cys
344
A
Leu
345
A
Leu
346
A
Asp
347
A
Arg
348
A
Val
349
A
Pro
350
A
Glu
351
A
Glu
352
A
Glu
353
A
Lys
354
A
Asp
355
A
Thr
356
A
Asn
357
A
Val
358
A
Gln
359
A
Val
360
A
Leu
361
A
Met
362
A
Val
363
A
Leu
364
A
Gly
365
A
Ala
366
A
Gly
367
A
Arg
368
A
Gly
369
A
Pro
370
A
Leu
371
A
Val
372
A
Asn
373
A
Ala
374
A
Ser
375
A
Leu
376
A
Arg
377
A
Ala
378
A
Ala
379
A
Lys
380
A
Gln
381
A
Ala
382
A
Asp
383
A
Arg
384
A
Arg
385
A
Ile
386
A
Lys
387
A
Leu
388
A
Tyr
389
A
Ala
390
A
Val
391
A
Glu
392
A
Lys
393
A
Asn
394
A
Pro
395
A
Asn
396
A
Ala
397
A
Val
398
A
Val
399
A
Thr
400
A
Leu
401
A
Glu
402
A
Asn
403
A
Trp
404
A
Gln
405
A
Phe
406
A
Glu
407
A
Glu
408
A
Trp
409
A
Gly
410
A
Ser
411
A
Gln
412
A
Val
413
A
Thr
414
A
Val
415
A
Val
416
A
Ser
417
A
Ser
418
A
Asp
419
A
Met
420
A
Arg
421
A
Glu
422
A
Trp
423
A
Val
424
A
Ala
425
A
Pro
426
A
Glu
427
A
Lys
428
A
Ala
429
A
Asp
430
A
Ile
431
A
Ile
432
A
Val
433
A
Ser
434
A
Glu
435
A
Leu
436
A
Leu
437
A
Gly
438
A
Ser
439
A
Phe
440
A
Ala
441
A
Asp
442
A
Asn
443
A
Glu
444
A
Leu
445
A
Ser
446
A
Pro
447
A
Glu
448
A
Cys
449
A
Leu
450
A
Asp
451
A
Gly
452
A
Ala
453
A
Gln
454
A
His
455
A
Phe
456
A
Leu
457
A
Lys
458
A
Asp
459
A
Asp
460
A
Gly
461
A
Val
462
A
Ser
463
A
Ile
464
A
Pro
465
A
Gly
466
A
Glu
467
A
Tyr
468
A
Thr
469
A
Ser
470
A
Phe
471
A
Leu
472
A
Ala
473
A
Pro
474
A
Ile
475
A
Ser
476
A
Ser
477
A
Ser
478
A
Lys
479
A
Leu
480
A
Tyr
481
A
Asn
482
A
Glu
483
A
Val
484
A
Arg
485
A
Ala
486
A
Cys
487
A
Arg
488
A
Glu
489
A
Lys
490
A
Asp
491
A
Arg
492
A
Asp
493
A
Pro
494
A
Glu
495
A
Ala
496
A
Gln
497
A
Phe
498
A
Glu
499
A
Met
500
A
Pro
501
A
Tyr
502
A
Val
503
A
Val
504
A
Arg
505
A
Leu
506
A
His
507
A
Asn
508
A
Phe
509
A
His
510
A
Gln
511
A
Leu
512
A
Ser
513
A
Ala
514
A
Pro
515
A
Gln
516
A
Pro
517
A
Cys
518
A
Phe
519
A
Thr
520
A
Phe
521
A
Ser
522
A
His
523
A
Pro
524
A
Asn
525
A
Arg
526
A
Asp
527
A
Pro
528
A
Met
529
A
Ile
530
A
Asp
531
A
Asn
532
A
Asn
533
A
Arg
534
A
Tyr
535
A
Cys
536
A
Thr
537
A
Leu
538
A
Glu
539
A
Phe
540
A
Pro
541
A
Val
542
A
Glu
543
A
Val
544
A
Asn
545
A
Thr
546
A
Val
547
A
Leu
548
A
His
549
A
Gly
550
A
Phe
551
A
Ala
552
A
Gly
553
A
Tyr
554
A
Phe
555
A
Glu
556
A
Thr
557
A
Val
558
A
Leu
559
A
Tyr
560
A
Gln
561
A
Asp
562
A
Ile
563
A
Thr
564
A
Leu
565
A
Ser
566
A
Ile
567
A
Arg
568
A
Pro
569
A
Glu
570
A
Thr
571
A
His
572
A
Ser
573
A
Pro
574
A
Gly
575
A
Met
576
A
Phe
577
A
Ser
578
A
Trp
579
A
Phe
580
A
Pro
581
A
Ile
582
A
Leu
583
A
Phe
584
A
Pro
585
A
Ile
586
A
Lys
587
A
Gln
588
A
Pro
589
A
Ile
590
A
Thr
591
A
Val
592
A
Arg
593
A
Glu
594
A
Gly
595
A
Gln
596
A
Thr
597
A
Ile
598
A
Cys
599
A
Val
600
A
Arg
601
A
Phe
602
A
Trp
603
A
Arg
604
A
Cys
605
A
Ser
606
A
Asn
607
A
Ser
608
A
Lys
609
A
Lys
610
A
Val
611
A
Trp
612
A
Tyr
613
A
Glu
614
A
Trp
615
A
Ala
616
A
Val
617
A
Thr
618
A
Ala
619
A
Pro
620
A
Val
621
A
Cys
622
A
Ser
623
A
Ala
624
A
Ile
625
A
His
626
A
Asn
627
A
Pro
628
A
Thr
629
A
Gly
630
A
Arg
631
A
Ser
632
A
Tyr
633
A
Thr
634
A
Ile
635
A
Gly
636
A
Leu
637
A-Arg-131.000.850.730.650.550.450.340.200.020.040.110.060.130.190.270.270.270.360.400.390.460.520.500.520.600.610.650.550.420.320.210.080.05-0.06-0.08-0.06-0.10-0.15-0.22-0.24-0.29-0.28-0.29-0.32-0.28-0.25-0.26-0.27-0.20-0.18-0.13-0.08-0.02-0.09-0.030.010.070.110.130.130.200.230.240.310.330.320.380.450.460.380.350.230.110.00-0.08-0.12-0.22-0.26-0.30-0.30-0.31-0.31-0.27-0.30-0.32-0.34-0.33-0.34-0.35-0.35-0.32-0.30-0.27-0.24-0.19-0.15-0.13-0.050.01-0.010.030.140.150.120.190.250.320.340.350.280.190.100.040.030.02-0.03-0.10-0.11-0.12-0.14-0.22-0.18-0.10-0.18-0.20-0.07-0.07-0.14-0.10-0.02-0.07-0.090.100.100.180.240.230.310.250.250.210.220.170.120.140.04-0.03-0.05-0.10-0.12-0.08-0.06-0.03-0.050.040.020.01-0.00-0.01-0.01-0.01-0.05-0.05-0.06-0.07-0.04-0.060.000.030.030.01-0.040.020.100.020.000.110.100.030.080.140.090.060.100.110.170.200.230.260.250.290.260.300.350.270.200.040.040.020.020.050.060.120.110.090.150.190.200.210.210.190.240.280.340.450.510.480.430.390.230.240.090.120.220.170.210.260.240.280.260.360.360.350.280.220.280.210.290.400.390.380.480.500.480.490.550.520.490.530.550.560.550.510.440.290.160.140.230.140.220.190.190.330.370.410.560.540.530.650.650.600.660.730.640.610.670.610.530.460.230.170.190.150.160.110.080.100.05-0.06-0.05-0.04-0.04-0.000.080.050.050.01-0.00-0.04-0.08-0.07-0.11-0.13-0.11-0.17-0.23-0.23-0.14-0.11-0.09-0.19-0.26-0.24-0.24-0.26-0.36-0.33-0.33-0.28-0.29-0.35-0.39-0.35-0.35-0.41-0.45-0.39-0.39-0.46-0.45-0.36-0.38-0.42-0.37-0.31-0.31-0.35-0.31-0.34-0.33-0.36-0.37-0.36-0.38-0.37-0.38-0.43-0.45-0.46-0.43-0.46-0.39-0.34-0.42-0.40-0.44-0.44-0.45-0.48-0.50-0.50-0.49-0.49-0.47-0.47-0.49-0.47-0.43-0.42-0.43-0.41-0.42-0.44-0.47-0.48-0.46-0.44-0.45-0.39-0.37-0.29-0.31-0.27-0.30-0.37-0.41-0.40-0.42-0.45-0.42-0.42-0.44-0.42-0.39-0.38-0.40-0.42-0.38-0.36-0.34-0.44-0.43-0.42-0.38-0.36-0.31-0.28-0.30-0.28-0.30-0.34-0.29-0.33-0.32-0.34-0.33-0.39-0.39-0.42-0.37-0.43-0.28-0.20-0.12-0.09-0.06-0.020.040.01-0.03-0.04-0.09-0.06-0.06-0.06-0.04-0.12-0.18-0.12-0.17-0.25-0.24-0.21-0.31-0.30-0.27-0.18-0.21-0.28-0.28-0.31-0.34-0.29-0.21-0.09-0.060.010.060.090.140.180.230.220.220.200.220.170.170.170.150.140.110.060.070.080.00-0.02-0.020.040.060.100.080.040.060.040.030.040.020.070.060.030.050.020.110.130.170.190.190.200.220.190.130.130.160.130.160.130.090.04-0.03-0.12-0.14-0.020.040.080.060.050.010.020.020.040.120.150.180.210.210.210.250.240.240.200.210.200.220.250.250.230.200.190.130.080.02-0.05-0.11-0.17-0.21-0.31-0.29-0.17-0.17-0.27-0.25-0.23-0.16-0.08-0.04-0.01-0.11-0.12-0.13-0.18-0.17-0.18-0.19-0.22-0.24-0.12-0.060.030.060.100.140.150.200.170.190.220.230.230.200.180.200.200.220.220.230.220.230.230.190.140.080.080.040.02-0.01-0.02-0.000.020.060.100.140.190.220.230.220.210.200.140.150.180.220.200.140.100.110.070.050.060.070.030.010.00-0.05-0.03
A-Val-140.851.000.890.740.600.500.360.19-0.010.010.070.010.070.130.200.210.230.310.360.370.440.500.490.510.590.620.650.560.410.310.170.01-0.04-0.19-0.18-0.11-0.14-0.25-0.34-0.39-0.43-0.41-0.41-0.42-0.32-0.26-0.29-0.31-0.18-0.17-0.12-0.14-0.15-0.10-0.12-0.09-0.04-0.010.020.030.100.130.160.230.260.260.330.430.440.350.300.160.05-0.03-0.11-0.14-0.28-0.33-0.38-0.38-0.37-0.36-0.30-0.32-0.35-0.38-0.37-0.39-0.42-0.46-0.42-0.39-0.39-0.37-0.29-0.26-0.25-0.15-0.06-0.10-0.080.060.080.030.110.190.260.290.300.270.210.070.000.01-0.00-0.05-0.10-0.18-0.17-0.20-0.28-0.25-0.16-0.25-0.27-0.13-0.12-0.18-0.13-0.04-0.09-0.090.120.070.150.200.180.270.240.270.220.250.210.160.190.02-0.06-0.06-0.13-0.18-0.12-0.11-0.10-0.070.010.00-0.020.040.03-0.01-0.04-0.06-0.11-0.11-0.10-0.06-0.060.030.040.060.090.020.040.120.03-0.000.100.10-0.000.040.110.050.000.040.050.140.160.220.240.240.310.290.350.430.340.300.130.120.080.060.110.140.220.200.180.240.290.290.280.300.260.280.310.380.480.560.570.510.490.310.300.180.230.290.240.270.310.280.320.290.380.400.410.360.290.350.280.390.500.480.480.590.610.580.600.660.610.570.610.620.640.650.580.500.320.190.150.210.110.230.190.230.390.400.480.570.550.550.660.670.630.690.770.680.640.730.690.600.500.240.180.180.130.140.090.080.160.13-0.020.040.070.050.070.170.150.170.120.110.080.050.070.01-0.010.01-0.08-0.18-0.18-0.10-0.07-0.04-0.15-0.22-0.23-0.19-0.21-0.34-0.33-0.31-0.27-0.29-0.34-0.39-0.36-0.36-0.43-0.48-0.44-0.43-0.51-0.51-0.41-0.42-0.48-0.44-0.37-0.34-0.44-0.42-0.44-0.43-0.45-0.44-0.40-0.43-0.47-0.50-0.53-0.52-0.52-0.45-0.47-0.35-0.29-0.39-0.36-0.41-0.40-0.43-0.44-0.49-0.52-0.51-0.52-0.56-0.56-0.56-0.56-0.55-0.52-0.53-0.54-0.54-0.56-0.58-0.54-0.51-0.48-0.46-0.37-0.34-0.26-0.30-0.28-0.31-0.36-0.40-0.40-0.44-0.45-0.44-0.46-0.48-0.45-0.44-0.44-0.46-0.46-0.42-0.41-0.41-0.49-0.45-0.42-0.36-0.32-0.24-0.19-0.28-0.30-0.27-0.33-0.27-0.32-0.34-0.36-0.37-0.45-0.46-0.46-0.35-0.42-0.23-0.08-0.000.020.000.030.100.070.01-0.03-0.08-0.06-0.04-0.08-0.04-0.09-0.15-0.12-0.15-0.20-0.23-0.20-0.36-0.34-0.30-0.21-0.25-0.31-0.33-0.30-0.33-0.29-0.22-0.09-0.06-0.010.050.100.130.160.230.240.260.250.280.250.250.270.270.250.230.210.200.200.130.100.070.120.150.170.180.170.180.130.160.140.150.190.170.120.130.080.180.190.230.230.210.200.200.150.070.080.110.090.160.130.100.07-0.03-0.11-0.13-0.000.050.090.060.07-0.08-0.07-0.010.070.100.150.150.180.180.160.210.190.210.180.180.190.240.270.280.300.250.230.160.080.03-0.05-0.11-0.16-0.19-0.32-0.30-0.19-0.18-0.29-0.25-0.22-0.17-0.06-0.020.01-0.11-0.14-0.14-0.19-0.18-0.16-0.17-0.18-0.19-0.04-0.010.060.130.200.230.250.290.250.260.270.270.250.200.160.180.160.180.180.220.200.230.230.220.180.140.150.110.100.060.080.110.130.160.190.230.260.270.260.230.200.190.150.170.230.270.260.240.210.200.170.160.180.220.160.140.130.090.09
A-Ser-150.730.891.000.800.650.570.440.280.080.090.180.110.180.240.300.310.330.420.440.440.510.560.520.520.590.660.720.630.480.390.270.120.10-0.06-0.06-0.01-0.07-0.16-0.24-0.28-0.34-0.33-0.34-0.35-0.28-0.23-0.25-0.26-0.16-0.14-0.08-0.10-0.11-0.06-0.030.010.060.100.130.140.220.250.250.320.360.360.410.500.510.420.390.260.150.06-0.01-0.05-0.19-0.24-0.30-0.30-0.30-0.29-0.25-0.28-0.30-0.33-0.31-0.33-0.37-0.38-0.34-0.32-0.31-0.26-0.20-0.17-0.15-0.050.03-0.020.020.130.150.110.190.270.330.350.370.350.280.140.070.050.060.00-0.05-0.11-0.12-0.16-0.23-0.18-0.11-0.20-0.21-0.06-0.07-0.14-0.080.01-0.06-0.070.110.080.180.250.230.320.300.340.270.300.230.170.220.02-0.06-0.05-0.11-0.21-0.16-0.14-0.13-0.060.03-0.01-0.030.01-0.04-0.07-0.12-0.13-0.16-0.15-0.13-0.05-0.070.050.060.040.070.020.060.110.020.010.110.090.020.080.130.070.050.090.090.160.190.220.270.260.330.310.390.430.350.250.090.05-0.00-0.040.040.050.130.130.110.160.210.220.230.280.210.240.290.360.470.570.560.510.450.290.270.140.150.210.150.190.220.210.260.230.310.320.290.230.170.240.190.300.400.400.400.510.540.510.530.600.540.510.560.600.640.650.610.510.350.220.170.200.090.180.150.160.320.380.440.530.490.480.590.580.520.590.670.560.540.650.590.500.460.240.170.170.130.120.060.030.080.07-0.050.000.020.020.040.120.110.120.090.100.070.040.04-0.02-0.04-0.05-0.13-0.23-0.21-0.11-0.09-0.04-0.15-0.28-0.26-0.22-0.26-0.38-0.36-0.34-0.29-0.30-0.35-0.41-0.38-0.37-0.45-0.49-0.44-0.42-0.51-0.50-0.40-0.41-0.47-0.43-0.35-0.33-0.42-0.37-0.41-0.39-0.42-0.45-0.43-0.44-0.46-0.48-0.51-0.53-0.54-0.50-0.53-0.42-0.36-0.45-0.42-0.46-0.43-0.45-0.48-0.54-0.55-0.53-0.55-0.58-0.56-0.56-0.57-0.54-0.50-0.50-0.51-0.54-0.56-0.58-0.58-0.55-0.52-0.51-0.44-0.41-0.33-0.36-0.32-0.35-0.40-0.44-0.44-0.47-0.50-0.48-0.49-0.51-0.49-0.47-0.47-0.48-0.49-0.44-0.44-0.44-0.52-0.49-0.47-0.42-0.38-0.31-0.26-0.31-0.31-0.30-0.35-0.30-0.35-0.36-0.37-0.37-0.45-0.45-0.46-0.40-0.46-0.28-0.11-0.020.030.000.030.100.060.02-0.00-0.05-0.04-0.07-0.06-0.01-0.09-0.17-0.10-0.13-0.23-0.26-0.23-0.39-0.34-0.29-0.19-0.23-0.30-0.32-0.30-0.34-0.29-0.20-0.07-0.030.030.080.130.170.180.240.230.230.220.260.220.220.250.260.230.220.230.220.210.150.110.070.120.150.170.200.200.180.120.140.120.160.190.170.100.090.030.140.140.190.190.180.190.200.160.080.100.140.130.190.160.130.09-0.01-0.09-0.12-0.010.010.060.010.04-0.10-0.080.030.120.150.200.200.220.220.190.220.200.190.120.140.160.220.250.270.280.250.230.170.100.04-0.03-0.10-0.15-0.19-0.32-0.31-0.19-0.22-0.32-0.28-0.24-0.18-0.08-0.04-0.01-0.12-0.17-0.16-0.21-0.20-0.20-0.21-0.20-0.21-0.06-0.040.050.130.190.230.250.300.280.270.270.270.250.200.150.150.150.180.200.230.220.250.260.250.230.180.190.150.120.080.090.130.160.190.220.260.290.290.280.240.210.200.150.180.240.300.300.270.240.230.210.190.210.220.180.160.140.090.08
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A-Asn-210.02-0.010.080.230.390.560.680.871.000.730.750.670.660.600.520.580.610.490.430.500.460.310.290.320.220.320.290.400.550.610.700.730.600.610.600.580.480.490.420.400.290.260.220.160.110.060.090.160.090.080.040.110.150.080.330.450.450.420.440.480.430.340.270.250.350.350.210.230.370.410.410.500.630.530.570.500.420.320.180.140.110.100.020.050.040.070.120.050.040.160.180.060.120.270.220.110.260.350.230.200.360.310.180.260.330.240.300.250.260.240.140.180.230.190.120.120.020.080.090.060.080.120.060.020.060.070.020.000.020.02-0.010.010.020.010.080.100.110.040.030.020.060.160.100.070.090.110.040.01-0.03-0.00-0.01-0.06-0.08-0.07-0.08-0.21-0.21-0.31-0.40-0.37-0.35-0.35-0.16-0.16-0.16-0.13-0.18-0.10-0.03-0.15-0.16-0.110.03-0.11-0.12-0.06-0.10-0.16-0.08-0.04-0.11-0.08-0.02-0.040.00-0.14-0.13-0.23-0.10-0.11-0.12-0.110.030.000.170.070.090.04-0.02-0.18-0.12-0.21-0.29-0.31-0.29-0.24-0.39-0.43-0.35-0.37-0.48-0.41-0.33-0.24-0.110.060.120.260.270.390.390.300.190.180.130.150.060.060.100.190.170.17-0.02-0.09-0.11-0.15-0.10-0.06-0.15-0.15-0.15-0.12-0.20-0.20-0.15-0.13-0.23-0.21-0.13-0.030.110.220.360.440.540.550.520.470.420.330.350.290.200.230.300.270.250.240.170.100.060.05-0.00-0.06-0.04-0.03-0.08-0.080.000.060.090.060.060.06-0.08-0.25-0.17-0.19-0.26-0.30-0.33-0.43-0.50-0.49-0.45-0.41-0.33-0.33-0.30-0.23-0.27-0.25-0.04-0.14-0.20-0.25-0.27-0.20-0.24-0.16-0.18-0.34-0.31-0.34-0.36-0.36-0.38-0.41-0.36-0.33-0.30-0.29-0.29-0.25-0.22-0.21-0.16-0.11-0.06-0.030.010.040.060.070.100.160.210.250.190.260.280.200.150.210.270.280.240.180.08-0.03-0.14-0.20-0.30-0.27-0.33-0.28-0.21-0.23-0.18-0.17-0.15-0.16-0.10-0.05-0.06-0.050.040.050.020.070.140.120.110.110.10-0.00-0.02-0.15-0.20-0.28-0.29-0.31-0.25-0.27-0.29-0.26-0.26-0.27-0.26-0.21-0.21-0.21-0.16-0.16-0.17-0.15-0.13-0.10-0.06-0.02-0.06-0.06-0.13-0.16-0.19-0.20-0.22-0.060.090.060.030.120.100.130.180.220.200.230.06-0.10-0.19-0.23-0.24-0.20-0.21-0.30-0.28-0.14-0.14-0.12-0.10-0.160.06-0.060.040.05-0.07-0.070.08-0.03-0.18-0.010.180.120.170.230.210.210.170.11-0.03-0.15-0.13-0.010.01-0.000.04-0.02-0.11-0.12-0.15-0.20-0.32-0.39-0.42-0.41-0.46-0.41-0.34-0.33-0.34-0.28-0.24-0.23-0.24-0.19-0.14-0.12-0.07-0.08-0.05-0.10-0.13-0.14-0.23-0.25-0.23-0.18-0.17-0.29-0.37-0.44-0.48-0.45-0.48-0.50-0.44-0.38-0.29-0.23-0.16-0.11-0.07-0.010.030.050.090.070.060.080.070.080.120.010.060.070.080.180.250.240.230.220.210.170.140.060.03-0.05-0.06-0.19-0.27-0.24-0.25-0.29-0.29-0.25-0.29-0.22-0.21-0.27-0.15-0.22-0.16-0.16-0.12-0.09-0.14-0.08-0.01-0.06-0.15-0.19-0.22-0.25-0.30-0.20-0.19-0.14-0.19-0.24-0.29-0.33-0.38-0.37-0.40-0.44-0.40-0.40-0.33-0.27-0.29-0.21-0.22-0.16-0.15-0.16-0.20-0.17-0.18-0.16-0.14-0.17-0.11-0.05-0.03-0.050.010.020.100.080.130.110.140.140.140.130.080.040.050.020.000.030.010.030.000.050.01-0.010.010.020.020.050.08-0.05-0.020.060.090.02-0.00-0.07-0.05-0.04-0.12-0.060.02

Table-3: Dynamic cross-correlation matrix. The full table is also available in text format, you need a proper text editor without line wrapping to look at this file: 4X61-best-metformin-SAM-docked-pH7_dccm.tab. Note: At most 10 rows of the DCCM are shown above. Change the tabrowsmax variable in the macro to adjust this number.

6. Additional files

The following additional files have been created:

6.1. The main data table

The main table contains all collected data in a single file. The column names match the names used above for graphs in plots and columns in tables. You can find a more detailed explanation of this table in the user manual at Recipes > Run a molecular dynamics simulation > Analyzing a trajectory. If you parse this file automatically, keep in mind that the number of columns can change any time, so you have to use the names in the first table row to find the columns of interest: 4X61-best-metformin-SAM-docked-pH7_analysis.tab

6.2. The structures

The time averaged structure in PDB format: 4X61-best-metformin-SAM-docked-pH7_average.pdb

The snapshot with the minimum solute energy. Either just the solute in PDB format 4X61-best-metformin-SAM-docked-pH7_energymin.pdb, or the complete system including solvent as a YASARA scene 4X61-best-metformin-SAM-docked-pH7_energymin.sce.

The last snapshot of the simulation. Either just the solute in PDB format 4X61-best-metformin-SAM-docked-pH7_last.pdb, or the complete system including solvent as a YASARA scene 4X61-best-metformin-SAM-docked-pH7_last.sce

6.3. The RMSF table

A table that lists the Root Mean Square Fluctuations [RMSFs] of all atoms in [A] is available here: 4X61-best-metformin-SAM-docked-pH7_rmsf.tab. The RMSFs have also been converted to B-factors and stored in the B-factor field of the time-average structure above.

4x61 and SAM + metformin ==> RMSF

RMSF for Calpha after 55 ns molecular dynamics

6.4. High resolution plots

To facilitate publication, high resolution versions of the plots above have been created with a 4:3 aspect ratio suited for printing in a single column of a typical journal article. Just look at the figure number above to find the right file:

4X61-best-metformin-SAM-docked-pH7_report_figure4_hires.png

4X61-best-metformin-SAM-docked-pH7_report_figure5_hires.png

4X61-best-metformin-SAM-docked-pH7_report_figure6_hires.png

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4X61-best-metformin-SAM-docked-pH7_report_figure9_hires.png

4X61-best-metformin-SAM-docked-pH7_report_figure10_hires.png

4X61-best-metformin-SAM-docked-pH7_report_figure11_hires.png

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