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PubMed2001

Classical molecular interaction potentials: improved setup procedure in molecular dynamics simulations of proteins.

The latest version of the classical molecular interaction potential (CMIP) has the ability to predict the position of crystallographic waters in several proteins with great accuracy. This article analyzes the ability of the CMIP functional to improve the setup procedure of the molecular system in molecular dynamics (MD) simulations of proteins. To this end, the CMIP strategy is used to include both water molecules and counterions in different protein systems. The structural details of the configurations sampled from trajectories obtained using the CMIP setup procedure are compared with those obtained from trajectories derived from a standard equilibration process. The results show that standard MD simulations can lead to artifactual results, which are avoided using the CMIP setup procedure. Because the CMIP is easy to implement at a low computational cost, it can be very useful in obtaining reliable MD trajectories.

Acetylcholinesterase↗

PubMed2001

Use of surface area computations to describe atom-atom interactions.

Accessible surface (ASA) and atomic contact (ACA) areas are powerful tools for protein structure analysis. However, their use for analysis purposes could be extended if a relationship between them and protein stability could be found. At present, this is the case only for ASAs, which have been used to assess the contribution of the hydrophobic effect to protein stability. In the present work we study whether there is a relationship between atomic contact areas and the free energy associated to atom-atom interactions. We utilise a model in which the contribution of atomic interactions to protein stability is expressed as a linear function of the accessible surface area buried between atom pairs. We assess the validity of this hypothesis, using a set of 124 lysozyme mutants (Matthews, 1995, Adv Protein Chem, 249-278) for which both the X-ray structure and the experimental stability are known. We tested this assumption for residue representations with increasing numbers of atom types. Our results indicate that for simple residue representations, with only 4 to 5 atom types, there is not a clear linear relationship between stability and buried accessible area. However, this relationship is observed for representations with 6 to 9 atom types, where gross heterogeneities in the atom type definition are eliminated. Finally, we also study a version of the linear model in which the atom- atom interactions are represented utilising a simple function for the buried accessible area, which may be useful for protein structure prediction studies.

Bacteriophage T4↗