Table of Contents
USES OF A MOLECULAR MECHANICS FORCE FIELD
USING THE PARAMETER SET
1) Surface exposure...
Problems...
2) Electrostatic potential...
and the spatial derivatives indicate...
Isopotential maps show where another charged molecule might interact...
Problems...
ENERGY CALCULATIONS
Example...
Such maps help explain...
Problems...
MOLECULAR MECHANICS MINIMIZATION
Minimization could be done by trial and error...
Or...
Problems...
Problems (cont.)...
Example… the Lysyl-aspartate dipeptide
Lysyl-aspartate dipeptide mimized...
REFINING STRUCTURES
Example, Homology Modeling:
The 5 X-ray Structures of Rubredoxin illustrate these ideas:
Steps of Homology Modeling
Then:
Next:
Finally...
Example, modeling one rubredoxin from another...
Once the new bond is shortened to an appropriate length…
How to evaluate the results?
Comparison of X-ray, NMR and Homology Modeled Structures
Lessons & Problems...
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Author: John E. Wampler
Email: wampler@bchiris.bmb.uga.edu
Home Page: http://bmbiris.bmb.uga.edu/wampler
References:
Solvation energies from surface and volume calculations:
W. G. Richards, P. M. King, & C. A. Reynolds (1989) "Solvation
effects," Protein Engineering 2, 319-327
A. A. Rashin & M. A> Bukatin (1994) "A view of thermodynamics of
hydration emerging from continuum studies," Biophys. Chem. 51,
167-192
A. A. Rashin & K. Namboodiri (1987) "A simple method for the
calculation of hydration enthalpies of polar molecules with
arbitrary shapes," J. Phys. Chem. 91, 6003-6012.
D. J. Giesen, C. J. Cramer & D. G. Truhlar (1994) "Entropic
contributions to free energies of solvation," J. Phys. Chem. 98,
4141-4147.
Physical docking:
D. J. Bacon & J. Moult (1992) "Docking by least squares fitting
of molecular surface patterns," J. Mol. Biol. 225, 849-858.
R. M. Jackson & M. J. E. Sternberg (1995) "A continuum model for
protein-protein interactions: applications to the docking
problem," J. Mol. Biol. 250, 258-275.
F. Jiang & S. -H Kim (1991) "Soft docking: matching of molecular
surface cubes," J. Mol. Biol. 219, 79-102.
B. K. Shoichet & I. D. Kuntz (1991) "Protein docking and
complementarity," J. Mol. Biol. 221, 327-346.
Brownian dynamics:
S. H. Northrup (1994) "Hydrodynamic motions of large molecules,"
Current Opinion in Structural Biology 4, 269-274.
S. H. Northrup & H. P. Erickson (1992) "Kinetics of protein
protein association explained by brownian dynamics computer-
simulation," PNAS (USA) 89, 3338-3342.
Minimization methods
P. R. Bevington, "Data Reduction and Error Analysis for Physical Sciences," McGraw-Hill Book Co., New York (1969).
W. H. Press, B. P. Flannery, S. A. Teukolsky, W. T. Vetterling, "Numerical Recipes, The Art of Scientific Computing," Cambridge University Press, Cambridge (1986).
Structure refinement using molecular mechanics:
P. K. Warme, N. Go & H. A. Scheraga (1972) "Refinement of X-ray
data on proteins," J. Comp. Phys. 9, 303-317.
A. T. Brunger, M. Karplus & G. A. Petsko (1989) "Crystallographic
refinement by simulated annealing," Acta Cryst. A45, 50-61.
M. Levitt & S. Lifson (1969) "Refinement of protein conformations
using a macromolecular energy minimization procedure," J. Mol.
Biol. 46, 269-279.
Homology modeling using molecular mechanics:
S. H. Bryant & C. E. Lawrence (1993) "An empirical energy
function for threading protein sequence through the folding
motif," Proteins 16, 92-112.
N. Srinivasan & T. L. Blundell (1993) "An evaluation of the
performance of an automated procedure for comparative modelling
of protein tertiary structure," Protein Engineering 6, 501-512.
D. E. Stewart, P. K. Weiner & J. E. Wampler (1987) "Prediction of
the structure of proteins using related structures, energy
minimization and computer graphics," J. Mol. Graphics 5, 133-140.
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