Efficiency of simulated annealing for peptides with increasing geometrical restrictions
✍ Scribed by Baysal, Canan; Meirovitch, Hagai
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 236 KB
- Volume
- 20
- Category
- Article
- ISSN
- 0192-8651
No coin nor oath required. For personal study only.
✦ Synopsis
Simulated annealing SA is a popular global minimizer that can conveniently be applied to complex macromolecular systems. Thus, a molecular dynamics or a Monte Carlo simulation starts at high temperature, which is decreased gradually, and the system is expected to reach the low-energy region on the potential energy surface of the molecule. However, in many cases this process is not efficient. Alternatively, the low-energy region can be reached more effectively by minimizing the energy of selected molecular structures generated along the simulation pathway. The efficiency of SA to locate energyminimized structures within 5 kcalrmol above the global energy minimum is studied as applied to three peptide models with increasing geometrical Ž . restrictions: 1 The linear pentapeptide Leu-enkephalin described by the ECEPP Ž . potential, 2 a cyclic hexapeptide described by the GROMOS force field energy Ž . E alone, and 3 the same cyclic peptide with E combined with a GRO GRO restraining potential based on 31 proton᎐proton restraints obtained from nuclear Ž . magnetic resonance NMR experiments. The efficiency of SA is compared to Ž . that of the Monte Carlo minimization MCM method of Li and Scheraga, and to Ž . our local torsional deformations LTD method for the conformational search of cyclic molecules. The results for the linear peptide show that SA provides a relatively weak guidance towards the most stable energy region; as expected, this guidance increases for the cyclic peptide and the cyclic peptide with NMR restraints. However, in general, MCM and LTD are significantly more efficient than SA as generators of low-energy minimized structures. This suggests that