This paper presents a novel guided genetic algorithm (GGA) for protein folding prediction (PFP) in 2D hydrophobic-hydrophilic (HP) by exploring the protein core formation concept. A proof of the shape for an optimal core is provided and a set of highly probable sub-conformations are defined which help to establish the guidelines to form the core boundary. A series of new operators including diagonal move and tilt move are defined to assist in implementing the guidelines. The underlying reasons for the failure in the folding prediction of relatively long sequences using Unger's genetic algorithm (GA) in 2D HP model are analysed and the new GGA is shown to overcome these limitations. The overall strategy incorporates a swing function that provides a mechanism to enable the GGA to test more potential solutions and also prevent it from developing a schema that may cause it to become trapped in local minima. While the guidelines do not force particular conformations, the result is a number of conformations for particular putative ground energy and superior prediction accuracy, endorsing the improved performance compared with other well established nondeterministic search approaches