Continuous protein models

In molecular pharmacology research an indirect proof of a structural model is possible by functional examinations, e.g., by molecular biological experiments. Well-selected site directed mutagenesis and their functional characterization allows confirmation or rejection of a molecular protein model. The process is organized as an iterative procedure, where the biological answer of suggested mutations is used to refine the model. The iteration continues until the model... 

The membrane reactor concept was demonstrated in laboratory scale a decade ago by Butterworth et al. (15) and by Chose and Kostick (16) in studies on the hydrolysis of starch and cellulose, respectively. Later on several publications have appeared describing the analogous, continuous conversion of various proteins into peptides intended for human nutrition (17-22). Among these works only that of laccobucci et al. (18) presents a quantitative model of the membrane reactor in continuous protein hydrolysis, and it is also the only demonstration of the practical feasibility of the concept in pilot plant scale. 

Valuable insights into the thermodynamics and mechanisms of protein assembly come from Monte Carlo and Brownian dynamics studies of simple, continuous protein-like models. For example, Rey and Skolnick... 

Reduced continuous-space models were also employed in studies of the various aspects of protein [27,139] or polypeptide [49,140,141] folding. 

MD production runs are just a continuation of the MD equilibrium and continue up to several nanoseconds. The results from the production runs can be used for docking studies or to determine changes in the secondary or tertiary structure of the target protein. Protein models refined with MD simulations consist of a library of structures with similar backbone geometry, but with different side-chain rotamers. These different structures are especially useful for molecular docking studies when the conformation of the protein and the orientation of the side chains are unknown. 

Figures 1A,B and 2A show the initial space-filling models of ribonuclease A and malate synthase, respectively, in CPK colors (atomic representation) or in grey (AA representation) plus the obtained surface dots in black. The surface dots represent the anhydrous protein contour as obtained by SIMS or AA-SIMS, respectively the dots cover the protein model continuously (in a few...

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