Computational Approaches to Protein Structure Design: beta-Bellin
Abstract
Based on the known principles that govern protein folding of polypeptide chains into antiparallel B-sheet structures, a small protein molecule, B-bellin, has been designed by Drs. Jane and David Richardson. In the current project, computer methods were used to evaluate the structure of B-bellin models and , more generally, to answer fundamental questions about the relations among molecular geometry, atomic potential energy, and static stability of B-sheeted proteins. Using CONGEN, a program for conformational search, macromolecular energy, minimization and dynamics calculations, the stereochemistry, molecular surface, B-sheet twist and properties of B-bellin were analyzed. To elucidate the role of backbone and side chains in turn twist, molecular dynamics simulations were done on beta-bellin and its variants where the prolines 8, 16, and 24 were replaced either with glycines or with D-prolines. The simulations indicated that the most frequent conformation of the turns, in the absence of hydrogen bonding, was the left-handed type I twist. L-proline in position 2 of the turn, aspirate at position 3, and N-O hydrogen bonds between position 1-4 reversed this tendency and induced the right-handed, type I twist instead. Our results make it possible, in principle, to design reverse turns of predetermined stereo chemistry in protein structures. Keywords: Protein engineering.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 23, 1989
- Accession Number
- ADA203097
Entities
People
- Jiri Novotny
Organizations
- Harvard Medical School