Artificial neural networks and simulated molecular evolution are potential tools for sequence-oriented protein design.

Abstract

The potential of artificial neural filter systems for feature extraction from amino acid sequences is discussed. Analysis of signal peptidase I cleavage-sites in protein precursor sequences serves as an example application. Trained neural networks can be used as the fitness function in an evolutionary protein design cycle termed 'simulated molecular evolution' which is an entirely computer-based method for the rational design of locally encoded amino acid sequence features. The design procedure itself is regarded as an optimization process which can follow several schemes. Gradient search, diffusive search, and evolution strategy have been compared with regard to their usefulness for optimization. It turns out that gradient search is well suited for optimization in smooth fitness landscapes without local minima, whereas evolution strategy seems to be a method of choice for optimization in a high-dimensional multimodal search space. This is concluded from optimization experiments using a multimodal example function.