Uphill unfolding of native protein conformations in cubic lattices

Abstract

We present results from simulations of unfolding in cubic lattices with two types of simplified energy functions, namely the Miyazawa–Jernigan (MJ) energy function and the hydrophobic-polar (HP) model. The simulations are executed on six benchmark problems for the MJ model proposed by Faisca and Plaxco [7] and ten well-known benchmark problems for the HP model devised by Beutler and Dill [2]. The unfolding procedure utilizes the pull-move set as a neighbourhood relation and a new population-based search method. For all sixteen benchmark problems we establish the existence of short pathways with monotonically increasing energy functions from ground states to contact-free unfolded states, which includes the three sequences with a high contact order number studied in the MJ model. The number of pull-move transitions (length of unfolding pathways) differs only slightly for the sixteen benchmark problems and ranges from 27 to 31 for both types of benchmarks. The computational effort of finding unfolding paths and subsequent refolding is discussed in the context of one-way functions.