Jumping low, jumping high: Controlling hopping in the protein energy surface

Abstract

The protein conformational space is characterized as a multi-dimensional funnel-like energy surface with conformations corresponding to the native state around the energy basin. The dimensionally and ruggedness of this energy surface are primary why computationally determining the biologically active or native state of a protein remains a difficult challenge. A common template among structure prediction protocols begins by sampling many local minima in the energy surface. Basin Hopping (BH) has emerged as a suitable framework for effectively sampling these coarse grained local minima. BH consists of a series structural perturbations followed by minimizations, forming a trajectory of local minima with the Metropolis criterion biasing it towards increasingly low-energy minima.