Theoretical models

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The term theoretical model refers to a molecular model obtained, wholly or in part, by the use of theory, such as homology modeling, energy minimization, molecular mechanics or molecular dynamics. Such theoretical models are distinguished from empirical models, which are usually obtained by X-ray crystallography or nuclear magnetic resonance (NMR).

The distinction between theoretical and empirical models is important because when theoretical models are compared with empirical models, the theoretical models often contain significant errors. In contrast, when the structure of a particular macromolecule is determined using empirical methods by different laboratories, or both by crystallography and NMR, the agreement is usually quite good.

Empirical Models

Methods for judging the reliability and quality of empirical models are discussed at Quality assessment for molecular models.

Homology Models

Homology models, also called comparative models, are obtained by folding a target protein sequence to fit an empirically-determined template model. The registration between residues in the target and template is determined by an amino acid sequence alignment. Errors or uncertainties in the sequence alignment result in errors or uncertainties in the homology model. Provided there is sufficient sequence identity between the target and template, the main chain in homology models is usually mostly correct. However, the positions of sidechains in homology models are usually incorrect.

Ab Initio Models

When there is no template with sufficient sequence identity to use for homology modeling, one can use ab initio or de novo folding theory to fold a protein sequence. Such theory has modest success for small protein chains (80 amino acids or less), but is generally unable to predict the fold for longer chains.