A Comparison of Structural and Dynamic Properties of Different Simulation Methods Applied to SH 3

The dynamic and static properties of molecular dynamics simulations using various methods for treating solvent were compared. The SH3 protein domain was chosen as a test case because of its small size and high surface-to-volume ratio. The simulations were analyzed in structural terms by examining crystal packing, distribution of polar residues, and conservation of secondary structure. In addition, the “essential dynamics" method was applied to compare each of the molecular dynamics trajectories with a full solvent simulation. This method proved to be a powerful tool for the comparison of large concerted atomic motions in SH3. It identified methods of simulation that yielded significantly different dynamic properties compared to the full solvent simulation. Simulating SH3 using the stochastic dynamics algorithm with a vacuum (reduced charge) force field produced properties close to those of the full solvent simulation. The application of a recently described solvation term did not improve the dynamic properties. The large concerted atomic motions in the full solvent simulation as revealed by the essential dynamics method were analyzed for possible biological implications. Two loops, which have been shown to be involved in ligand binding, were seen to move in concert to open and close the ligand-binding site.

[1]  Eric Westhof,et al.  MULTIPLE MOLECULAR DYNAMICS SIMULATIONS OF THE ANTICODON LOOP OF TRNAASP IN AQUEOUS SOLUTION WITH COUNTERIONS , 1995 .

[2]  G Vriend,et al.  The essential dynamics of thermolysin: Confirmation of the hinge‐bending motion and comparison of simulations in vacuum and water , 1995, Proteins.

[3]  Andrea Musacchio,et al.  High-resolution crystal structures of tyrosine kinase SH3 domains complexed with proline-rich peptides , 1994, Nature Structural Biology.

[4]  Hongtao Yu,et al.  Structural basis for the binding of proline-rich peptides to SH3 domains , 1994, Cell.

[5]  Herman J. C. Berendsen,et al.  A Molecular Dynamics Study of the Decane/Water Interface , 1993 .

[6]  C. Sander,et al.  An effective solvation term based on atomic occupancies for use in protein simulations , 1993 .

[7]  M. Saraste,et al.  Crystal structure of the SH3 domain in human Fyn; comparison of the three‐dimensional structures of SH3 domains in tyrosine kinases and spectrin. , 1993, The EMBO journal.

[8]  C. Sander,et al.  Quality control of protein models : directional atomic contact analysis , 1993 .

[9]  Andrea Musacchio,et al.  Crystal structure of a Src-homology 3 (SH3) domain , 1992, Nature.

[10]  García,et al.  Large-amplitude nonlinear motions in proteins. , 1992, Physical review letters.

[11]  G Vriend,et al.  WHAT IF: a molecular modeling and drug design program. , 1990, Journal of molecular graphics.

[12]  C Sander,et al.  Polarity as a criterion in protein design. , 1989, Protein engineering.

[13]  Wang Lu,et al.  ON THE APPROXIMATION OF SOLVENT EFFECTS ON THE CONFORMATION AND DYNAMICS OF CYCLOSPORIN A BY STOCHASTIC DYNAMICS SIMULATION TECHNIQUES , 1988 .

[14]  H. Berendsen,et al.  A LEAP-FROG ALGORITHM FOR STOCHASTIC DYNAMICS , 1988 .

[15]  W. Kabsch,et al.  Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical features , 1983, Biopolymers.

[16]  H. Berendsen,et al.  Interaction Models for Water in Relation to Protein Hydration , 1981 .

[17]  G. Ciccotti,et al.  Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes , 1977 .