CHARMM minimization

Table 3 Performance Among Three CHARMM Minimizers on Two Molecular Systems...

Figure 5 Minimization progress (gradient norm) of three CHARMM minimizers for (a) alanine dipeptide and (b) lysozyme. See Table 3...

Bernhard R. Brooks, Robert E. Bruccoleri, Barry D. Olafson, David J. States, S. Swaminathan, and Martin Karplus. CHARMM A program for macro-molecular energy, minimization, and dynamics calculations. J. Comp. Chem., 4(2) 187-217, 1983. 

Watanabe, M., Karplus, M. Dynamics of Molecules with Internal Degrees of Freedom by Multiple Time-Step Methods. J. Chem. Phys. 99 (1995) 8063-8074 Figueirido, F., Levy, R. M., Zhou, R., Berne, B. J. Large Scale Simulation of Macromolecules in Solution Combining the Periodic Fast Multiple Method with Multiple Time Step Integrators. J. Chem. Phys. 106 (1997) 9835-9849 Derreumaux, P., Zhang, G., Schlick, T, Brooks, B.R. A Truncated Newton Minimizer Adapted for CHARMM and Biomolecular Applications. J. Comp. Chem. 15 (1994) 532-555... 

Brooks, B.R. Bruccoleri, R.E. Olafson, B.D. States, D.J. Swaminathan, S. Karpins, M. CHARMM A program for macromolecular energy, minimization, and dynamics calculations J. Comput. Chem. 4 187-217, 1983. 

Of the biomolecular force fields, AMBER [21] is considered to be transferable, whereas academic CHARMM [20] is not transferable. Considering the simplistic form of the potential energy functions used in these force fields, the extent of transferability should be considered to be minimal, as has been shown recently [52]. As stated above, the user should perform suitable tests on any novel compounds to ensure that the force field is treating the systems of interest with sufficient accuracy. 

Brooks R, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M (1983) Charmm A program for macromolecular energy minimization and dynamics calculations. J Comput Chem 4 187-217. 

From the starting structures (PDB file), the full complement of hydrogens is added using a utility within CHARMM. The entire protein is then solvated within a sphere of TIP3P model waters, with radius such that all parts of the protein were solvated to a depth of at least 5 A. A quartic confining potential localized on the surface of the spherical droplet prevented evaporation of any of the waters during the course of the trajectory. The fully solvated protein structure is energy minimized and equilibrated before the production simulation. 

If necessary, the optimized structures can be subjected to additional energy minimization separately (outside CORCEMA-ST) using standard force field parameters in programs such as AMBER or CHARMM. 

Fig. 3. Energy-minimized molecular structure (CHARMm ver. 23) of cyclofprolyl-glycine),...

As shown by a flowchart in Figure 1, the method is fully automated, although certain critical parameters (e.g., number of replicas, radius of the sphere for random distribution, CHARMM parameters for the minimization) can be adjusted by the user to optimize it for specific applications. Several thousand replicas of a given group are randomly distributed inside a sphere... 

We thank J. Apostolakis and Professor A. Pluckthun for helpful discussions. The calculations were performed on an SGI Indigo2 and an eight-processor SGI Challenge (R4400 processors). The CHARMM program within the version 4.0 of the QUANTA software package (Biosym-MSI Inc) was used for some of the minimization performed in this work. The CCLD program is available from A. Caflisch. 

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