Exploring Conformational Space Using Simulation Methods

6 Exploring Conformational Space Using Simulation Methods 

The Monte Carlo and molecular dynamics simulation methods can be used to explore the conformational space of molecules. During such a simulation the system is able to 

A comparison of various methods for searching conformational space has been performed for cycloheptadecane (C17H34) [Saunders et al. 1990]. The methods compared were the systematic search, random search (both Cartesian and torsional), distance geometry and molecular dynamics. The number of unique minimum energy conformations found with each method within 3 kcal/mol of the global minimum after 30 days of computer processing were determined (the study was performed in 1990 on what would now be considered a very slow computer). The results are shown in Table 9.1. 

Method Total unique conformers found after 30 days processing 

---

When no structural data are available for the receptor, methods that explore conformational space using techniques such as simulated annealing and cluster analysis may find the best match between various ligands. During this procedure,low energy conformers are selected and minimized pairwise, and the best match obtained from all different conformations can be selected. This method is useful for structurally dissimilar ligands. 

Exploration of the conformational space of protein models could be done using different computational techniques. These include MD [21], Brownian dynamics [22,23], Monte Carlo methods [24-27], and other simulation or optimization techniques such as genetic algorithms [25,28-31]. 

Within the last decade important progress has been made in the reliability of MD simulations of solvated nucleic acids using improved force fields and, in particular, a better treatment of electrostatics by the particle-mesh Ewald method. For the first time unrestrained simulations have become possible. Starting out firom experimental geometries it is now possible to explore the conformational space in the vicinity of the starting geometry and to study conformational transitions. ... 

---