Susan Khor

Susan Khor

A method that reconstructs protein residue networks using suitable node selection and edge recovery policies produced numerical observations that correlate strongly (Pearson's correlation coefficient < -0.83) with published folding rates for 52 two-state folders and 21 multi-state folders; correlations are also strong at the fold-family level. These results were obtained serendipitously with the ND model, which was introduced previously, but is here extended with policies that dictate actions according to feature states. This result points to the importance of both the starting search point and the prevailing condition (random seed) for the quick success of policy search by a simple hill-climber. The two conditions, suitable policies and random seed, which (evidenced by the strong correlation statistic) setup a conducive environment for modelling protein folding within ND, could be compared to appropriate physiological conditions required by proteins to fold naturally. Of interest is an examination of the sequence of restored edges for potential as plausible protein folding pathways. Towards this end, trajectory data is collected for analysis and further model evaluation and development.

Susan Khor

An algorithm (bliss) is proposed to speed up the construction of slow adaptive walks. Slow adaptive walks are adaptive walks biased towards closer points or smaller move steps. They were previously introduced to explore a search space, e.g. to detect potential local optima or to assess the ruggedness of a fitness landscape. To avoid the quadratic cost of computing Hamming distance (HD) for all-pairs of strings in a set in order to find the set of closest strings for each string, strings are sorted and clustered by bliss such that similar strings are more likely to get paired off for HD computation. To efficiently arrange the strings by similarity, bliss employs the idea of shared non-overlapping position specific subsequences between strings which is inspired by an alignment-free protein sequence comparison algorithm. Tests are performed to evaluate the quality of b-walks, i.e. slow adaptive walks constructed from the output of bliss, on enumerated search spaces. Finally, b-walks are applied to explore larger search spaces with the help of Wang-Landau sampling.