The Application of Hybridized Genetic Algorithms to the Protein Folding Problem

The protein folding problem consists of attempting to determine the native conformation of a protein given its primary structure. This study examines various methods of hybridizing a genetic algorithm implementation in order to minimize an energy function and predict the conformation (structure) of Met-enkephalin. Genetic Algorithms are semi-optimal algorithms designed to explore and exploit a search space. The genetic algorithm uses selection, recombination, and mutation operators on populations of strings which represent possible solutions to the given problem. One step in solving the protein folding problem is the design of efficient energy minimization techniques. A conjugate gradient minimization technique is described and tested with different replacement frequencies. Baidwinian, Lamarckian, and probabilistic Lamarckian evolution are all tested. Another extension of simple genetic algorithms can be accomplished with niching. Niching works by de-emphasizing solutions based on their proximity to other solutions in the space. Several variations of niching are tested. Experiments are conducted to determine the benefits of each hybridization technique versus each other and versus the genetic algorithm by itself. The experiments are geared toward trying to find the lowest possible energy and hence the minimum conformation of Met-enkephalin. In the experiments, probabilistic Lamarckian strategies were successful in achieving energies below that of the published minimum in QUANTA

Analysis of Linkage-Friendly Genetic Algorithms

Evolutionary algorithms (EAs) are stochastic population-based algorithms inspired by the natural processes of selection, mutation, and recombination. EAs are often employed as optimum seeking techniques. A formal framework for EAs is proposed, in which evolutionary operators are viewed as mappings from parameter spaces to spaces of random functions. Formal definitions within this framework capture the distinguishing characteristics of the classes of recombination, mutation, and selection operators. EAs which use strictly invariant selection operators and order invariant representation schemes comprise the class of linkage-friendly genetic algorithms (lfGAs). Fast messy genetic algorithms (fmGAs) are lfGAs which use binary tournament selection (BTS) with thresholding, periodic filtering of a fixed number of randomly selected genes from each individual, and generalized single-point crossover. Probabilistic variants of thresholding and filtering are proposed. EAs using the probabilistic operators are generalized fmGAs (gfmGAs). A dynamical systems model of lfGAs is developed which permits prediction of expected effectiveness. BTS with probabilistic thresholding is modeled at various levels of abstraction as a Markov chain. Transitions at the most detailed level involve decisions between classes of individuals. The probability of correct decision making is related to appropriate maximal order statistics, the distributions of which are obtained. Existing filtering models are extended to include probabilistic individual lengths. Sensitivity of lfGA effectiveness to exogenous parameters limits practical applications. The lfGA parameter selection problem is formally posed as a constrained optimization problem in which the cost functional is related to expected effectiveness. Kuhn-Tucker conditions for the optimality of gfmGA parameters are derived