Theoretical studies of the response of a protein structure to cavity-creating mutations.
We have investigated the response of a protein structure to cavity-creating mutations by molecular dynamics (MD) simulations for the wild-type and the five mutants of phage T4 lysozyme. Essential dynamics (ED) analysis and the methods for calculating different components of local interaction energies are used to examine the structural and energetic characteristics associated with the mutations. In agreement with the x-ray results, it is found that the structural changes due to the replacements of a bulky side chain such as Leu or Phe with Ala within the hydrophobic core can be characterized as slight adjustments rather than substantial reorganization of the protein. The relative stability of different mutant structures can be related with the extent of structural readjustments in response to the mutation. The destabilization of the mutant Leu-->Ala proteins relative to the wild-type is closely related with the loss of van der Waals contacts due to the cavity-creating mutations.
Lee
J
J
Department of Chemistry and Center for Molecular Catalysis, Seoul National University, Seoul 151-742, Korea.
Lee
K
K
Shin
S
S
D019943:Amino Acid Substitution; D017122:Bacteriophage T4 / Q000201:enzymology / Q000235:genetics; D055592:Biophysical Phenomena; D001703:Biophysics; D004795:Enzyme Stability; D009113:Muramidase / Q000737:chemistry* / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D017510:Protein Folding; D055672:Static Electricity; D013816:Thermodynamics
D009113:Muramidase