Lattice simulations of aggregation funnels for protein folding.
A computer model of protein aggregation competing with productive folding is proposed. Our model adapts techniques from lattice Monte Carlo studies of protein folding to the problem of aggregation. However, rather than starting with a single string of residues, we allow independently folding strings to undergo collisions and consider their interactions in different orientations. We first present some background into the nature and significance of protein aggregation and the use of lattice Monte Carlo simulations in understanding other aspects of protein folding. The results of a series of simulation experiments involving simple versions of the model illustrate the importance of considering aggregation in simulations of protein folding and provide some preliminary understanding of the characteristics of the model. Finally, we discuss the value of the model in general and of our particular design decisions and experiments. We conclude that computer simulation techniques developed to study protein folding can provide insights into protein aggregation, and that a better understanding of aggregation may in turn provide new insights into and constraints on the more general protein folding problem.
Department of Algorithms and Discrete Mathematics, Sandia National Laboratories, Albuquerque, New Mexico 87185, USA. scistra@cs.sandia.gov
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D000465:Algorithms; D003198:Computer Simulation; D006860:Hydrogen Bonding; D009010:Monte Carlo Method; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012995:Solubility; D012997:Solvents; D013816:Thermodynamics; D013997:Time Factors
D011506:Proteins; D012997:Solvents