Effects of side-chain packing on the formation of secondary structuresin protein folding

摘要

We have recently shown that protein folding is driven by the water-entropy gain. When the a-helixorβ-sheet is formed, the excluded volumes generated by the backbone and side chains overlap,leading to an increase in the total volume available to the translational displacement of watermolecules. Primarily by this effect, the water entropy becomes higher. At the same time, thedehydration penalty (i.e., the break of hydrogen bonds with water molecules) is compensated by theformation of intramolecular hydrogen bonds. Hence, these secondary structures are veryadvantageous units, which are to be formed as much as possible in protein folding. The packing ofside chains, which leads to a large increase in the water entropy, is also crucially important. Here weinvestigate the roles of the side-chain packing in the second structural preference in protein folding.For some proteins we calculate the hydration entropies of a number of structures including thenative structure with or without side chains. A hybrid of the angle-dependent integral equationtheory combined with the multipolar water model and the morphometric approach is employed inthe calculation. Our major findings are as follows. For the structures without side chains, there is anapparent tendency that the water entropy becomes higher as the a-helix or β-sheet content increases.For the structures with side chains, however, a higher content of a-helices or β-sheets does notnecessarily lead to larger entropy of water due to the effect of the side-chain packing. The thorough,overall packing of side chains, which gives little space in the interior, is unique to the nativestructure. To accomplish such specific packing, the a-helix and β-sheet contents are prudentlyadjusted in protein folding.