Uses of simple minimization 1. The"minimum perturbation approach"to modeling a mutation Assume structure of single-site mutant is close to known Wild-type structure Find stable conformations for mutant side chain in context of wild-type protein Use energy minimization to relax candidate structures (all degrees of freedom) Shih, brady and Karplus, Proc. Nat. Acad. Sci. USA82: 1697-1700 (1985); hemagglutinin Gly to Asp mutation modeled accurately 2. Relieving strain before analyZing the energy of an experimental or predicted structure 3. Structure building and refinement when solving structures using X-ray crystallography or NMRUses of simple minimization 1. The “minimum perturbation approach” to modeling a mutation – Assume structure of single-site mutant is close to known wild-type structure • Find stable conformations for mutant side chain in context of wild-type protein • Use energy minimization to relax candidate structures (all degrees of freedom) Shih, Brady, and Karplus, Proc. Natl. Acad. Sci. USA 82: 1697–1700 (1985); hemagglutinin Gly to Asp mutation modeled accurately 2. Relieving strain before analyzing the energy of an experimental or predicted structure 3. Structure building and refinement when solving structures using X-ray crystallography or NMR