STRUCTURE, DYNAMICS AND ENERGETICS OF INITIATION SITES IN PROTEIN-FOLDING .1. ANALYSIS OF A 1-NS MOLECULAR-DYNAMICS TRAJECTORY OF AN EARLY FOLDING UNIT IN WATER - THE HELIX-I LOOP-I FRAGMENT OF BARNASE

The dynamic and energetic behavior of an initiation site of protein fo lding (helix I/loop I fragment of barnase) isolated from the tertiary environment of the rest protein is investigated in a 1 ns molecular dy namics simulation. All atom representation, explicit solvent descripti on, and periodic boundary conditions are applied. In the course of the simulation several steps of structural disintegration are observed, f ollowed by events partially rebuilding the initial structure. The phas e of disintegration results in a fragment conformation completely lack ing hydrogen bonds, with one residue in the center of the helix change d from alpha to beta conformation. The transition state of helix disin tegration is characterized by a complete i-->i+4/i+5 hydrogen bonding network which undergoes gradual hydrolysis starting at the solvent exp osed flank and proceeding towards the interior of the fragment perpend icular to the axis of the helix. Energetic analysis of the helix trans itions shows that the i-->i+4/i-->i+5 network of hydrogen bonds accomm odates one helical residue in beta conformation with only slightly wor se hydrogen bonding energy and Van der Waals packing compared to the r egular alpha-helix. The stability of the fragment is primarily due to hydrophobic interactions of residues shown to be essential in mutagene sis experiments.