Wykład 4.pdf

(127 KB) Pobierz
Molecular Dynamics
Lecture 4: GROMACS overview
D
M
A
T
y
b
-
3
1
0
2
Problems encountered while choosing initial structure
1
2
3
X-ray: low resolution, incomplete or mutated residues
NMR: which structure?
homology modelling: reliability
D
M
A
T
y
b
-
3
1
0
2
Problems encountered while choosing initial structure
inserting and/or repairing residues (manually or by using
specialized software, e.g. WHATIF, Quanta, SwissViewer)
what is the protonation state of some residues (pK
a
)? -
important for binding sites, may dramatically influence
stability of the protein during modelling
D
M
A
T
y
b
-
3
1
0
2
Discussion on the quality of the experimental data
Each experiment involves averaging over space and time
(molecule), thus giving average distribution
Different distributions of electron density may lead to the
same average value
Single structures cannot represent set of different
conformations descibed by Maxwell-Boltzmann distribution
At present experimental results are often not accurate
enough, e.g. for testing force fields
D
M
A
T
y
b
-
3
1
0
2
Discussion on the quality of measurements results
calculated data should be compared directly with the
corresponding measured data (NOE,
3
J) and not with
indirect structural parameters like bond lengths, angles etc.
Experimental values should be converged gradually to
accurate computational values - for example MD calculations
using GROMOS force field without NMR restrains does
reproduce experimental NOE/
3
J values bettter than a set of
20 structures obtained from NMR/XPLOR.
D
M
A
T
y
b
-
3
1
0
2

Plik z chomika:

Inne pliki z tego folderu:

Inne foldery tego chomika:

Zgłoś jeśli naruszono regulamin