Minimum energy structure , protein

These initial configurations can represent a minimum energy structure either from another simulation (i.e., a final structure from a energy minimization in a quantum or classical Monte Carlo simulation can be used as the starting state for classical simulations), from experimental observation (i.e., the pdb database for crystallographic structures of proteins) or building the initial coordinates based upon the equilibrium bond distances and bond angles from the force-field. 

The most ambitious approaches to the protein folding problem attempt to solve it from firs principles (ab initio). As such, the problem is to explore the coirformational space of th molecule in order to identify the most appropriate structure. The total number of possibl conformations is invariably very large and so it is usual to try to find only the very lowes energy structure(s). Some form of empirical force field is usually used, often augmente with a solvation term (see Section 11.12). The global minimum in the energy function i assumed to correspond to the naturally occurring structure of the molecule. 

Classical electrostatic modeling based on the Coulomb equation demonstrated that the model system chosen could account for as much as 85% of the effect of the protein electric field on the reactants. Several preliminary computations were, moreover, required to establish the correct H-bond pattern of the catalytic water molecule (WAT in Fig. 2.6). Actually, in the crystal structure of Cdc42-GAP complex [60] the resolution of 2.10 A did not enable determination of the positions of the hydrogen atoms. Thus, in principle, the catalytic water molecule could establish several different H-bond patterns with the amino acids of the protein-active site. Both classical and quantum mechanical calculations showed that WAT, in its minimum-energy conformation,... 

The simplest of these approaches includes Gaussian Network Models (GNM) or Elastic Network Models (ENM) which assume that the native state represents the minimum energy configuration. A structure is represented as a network of beads connected by harmonic springs.12,13 One bead represents one residue and is usually centered on the position of the Ca carbon. Single parameter harmonic interactions are assigned to bead pairs which fall within a certain cutoff distance Rc. In case of proteins, Rc is usually around 8-10 A. The representation of the molecule in the... 

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