USES OF A MOLECULAR MECHANICS FORCE FIELD

Table of Contents

{1} USES OF A MOLECULAR MECHANICS FORCE FIELD

{2} USING THE PARAMETER SET

{3} 1) Surface exposure...

{4} Problems...

{5} 2) Isopotential maps show where another charged molecule might interact...

{6} Problems...

{7} USING THE MOLECULAR MECHANICS ENERGY

{8} To investigate “cost” of changes in conformation.

{9} Such maps help explain the Ramachandran plots of proteins where only X-gly phi angles (?) can be in the region of phio. Of course, the proline (?) phi angle is restricted by a covalent bond.

{10} To evaluate nature of intramolecular interactions.

{11} To calculate heats of formation (class 2).

{12} Problems...

{13} USING THE SPATIAL DERIVATIVES

{14} First and Second Derivatives of some common force field functions (adapted from Niketic & Rasmussen, 1977)

{15} First and Second Derivatives of common force field functions (adapted from Niketic & Rasmussen, 1977)

{16} Converting to Cartesian force components...

{17} Numerical derivatives...

{18} USING THE SPATIAL FIRST DERIVATIVE

{19} Minimization could be done by trial and error...

{20} Minimization won’t “climb over” energy barriers

{21} Molecular Dynamics

{22} The MD Process…

{23} 3) EQUILIBRATION

{24} The result is a collection of structures, single “frames” along the motion trajectory.

{25} What about the 2nd derivatives?

{26} A minimum in 2 dimensions could also a “saddle point”

{27} With many dimensions, the table (matrix) of second derivatives can also distinquish minima from maxima and saddle points...

{28} Using the 2nd derivatives...

Email: wampler@bchiris.bmb.uga.edu

Home Page: http://bmbiris.bmb.uga.edu/BMB8200

References:

Cannon, J. F. (1993) "AMBER Force-field parameters for Guanosine-Triphosphate and its Imido and Methylene Analogs," J. Comp. Chem. 14, 995-1005.

Niketic, S. R., and K. Rasmussen (1977) The Consistent Force Field: A Documentation, Springer-Verlag, Berlin.

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.

Pedro N. L. Palma (1998), "Studies of Macromolecular Recognition and Prediction of Redox Properties of Metalloproteins," Doctoral Dissertation, Universidade Nova de Lisboa, Portugal.

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.

The Molecular Mechanics Reference List