USES OF A MOLECULAR MECHANICS FORCE FIELD

Table of Contents

USES OF A MOLECULAR MECHANICS FORCE FIELD

USING THE PARAMETER SET

1) Surface exposure...

Problems...

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

Problems...

USING THE MOLECULAR MECHANICS ENERGY

To investigate “cost” of changes in conformation.

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.

To evaluate nature of intramolecular interactions.

To calculate heats of formation (class 2).

Problems...

USING THE SPATIAL DERIVATIVES

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

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

Converting to Cartesian force components...

Numerical derivatives...

USING THE SPATIAL FIRST DERIVATIVE

Minimization...

Minimization could be done by trial and error...

Minimization won’t “climb over” energy barriers

Molecular Dynamics

The MD Process…

3) EQUILIBRATION

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

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