SDM

SDM predicts the impact of non-synonymous single nucleotide polymorphisms on protein stability and function by estimating free energy differences between wild-type and mutant proteins.

Key Features:

• Local Structural Environment Analysis: Reports the structural context surrounding wild-type and mutant residues to assess local effects of mutations.
• Stability Score Prediction: Calculates a numerical stability score reflecting the predicted change in protein stability between wild-type and mutant proteins.
• Disease Association Prediction: Provides an assessment of whether mutations may be associated with disease based on predicted effects on protein function.
• Environment-specific Substitution Frequencies: Utilizes environment-specific amino acid substitution frequencies derived from homologous protein families.
• Statistical Potential Energy Functions: Applies statistical potential energy functions to relate substitution frequencies to stability changes.

Scientific Applications:

• Variant Effect Assessment: Evaluation of non-synonymous SNPs to predict their effects on protein stability and function when experimental characterization is impractical.
• Disease Variant Prioritization: Prioritization of mutations that are more likely to be deleterious or disease-associated based on predicted structural and stability changes.
• Structural Interpretation of Mutations: Interpretation of how single-residue changes may alter local structural environments within proteins.

Methodology:

Calculates a stability score representing the free energy difference between wild-type and mutant proteins using environment-specific amino acid substitution frequencies derived from homologous protein families and statistical potential energy functions.