Hydrophobic core of the villin headpiece protein

Abstract

We study the formation of the hydrophobic core for a villin headpiece 36-residue protein (HP-36) by using the successive time frames for the all-atom coordinates (as functions of the time-step index j) obtained from action-derived molecular dynamics simulations. In an aqueous environment, the side chains of its hydrophobic residues gather to form a hydrophobic core, driving HP-36 to fold into the stable native structure. The hydrophobic core of HP-36 consists of the side chains of five hydrophobic residues, Phe7, Phe11, Phe18, Leu21, and Leu29, in its folded native structure. We directly measure the distances between the side chains of the five hydrophobic residues in the hydrophobic core of HP-36 from the straightly-extended structure (j = 0) to the folded native structure (j = 2000) in order to find when the hydrophobic core is formed and becomes stable. In a very early folding stage, these distances reduce quickly, leading to a rapid compaction. This very early compaction is not stable because the distances between the side chains of three phenylalanines expand prominently later. At the end of early folding stage (j 1000), these distances show some expansion around j ∼ 1200, and they gradually approach their final values after that expansion.