The relationship between sequence and structure divergence in homologous proteins is explored. Homologous proteins have regions with the same general fold and regions with different folds. For distantly related proteins (residue identity ~20%), the regions with the same fold may comprise less than half of each molecule. The structural differences in these regions increase as the amino acid sequences diverge. The root mean square deviation (Δ) in the positions of main chain atoms is related to the fraction of mutated residues (H) by the equation Δ(Å) = 0.40 e^(1.87H). The study compares structures from eight protein families, using atomic coordinates of 25 proteins. These structures have high resolution and are refined. The common core of homologous proteins consists of regions with the same fold, including major elements of secondary structure and active site peptides. The size of the common core decreases as sequence identity decreases. Proteins with β-sheets have smaller common cores compared to those with α-helices. Structural divergence in the common cores is measured by Δ, which varies between 0.62 and 2.31 Å for 32 homologous pairs. The value of Δ depends on the procedure used to define the common cores. The exponential relationship between sequence identity (H) and Δ is given by Δ = 0.40 e^(1.87H). This relationship arises because proteins accept mutations of surface residues more readily than buried residues. Closely related proteins differ mainly in surface residues, while distantly related proteins differ in both surface and buried residues. The results show that the extent of structural changes is directly related to the extent of sequence differences. The degree of success in predicting the structure of a protein from its sequence using an homologous protein depends on the sequence identity. Proteins with >50% sequence homology have close structural models, while those with 20% homology show large structural differences. However, the active sites of distantly related proteins can have similar geometries due to evolutionary structural changes. The study highlights the importance of sequence identity in predicting protein structure and the role of structural changes in evolution.The relationship between sequence and structure divergence in homologous proteins is explored. Homologous proteins have regions with the same general fold and regions with different folds. For distantly related proteins (residue identity ~20%), the regions with the same fold may comprise less than half of each molecule. The structural differences in these regions increase as the amino acid sequences diverge. The root mean square deviation (Δ) in the positions of main chain atoms is related to the fraction of mutated residues (H) by the equation Δ(Å) = 0.40 e^(1.87H). The study compares structures from eight protein families, using atomic coordinates of 25 proteins. These structures have high resolution and are refined. The common core of homologous proteins consists of regions with the same fold, including major elements of secondary structure and active site peptides. The size of the common core decreases as sequence identity decreases. Proteins with β-sheets have smaller common cores compared to those with α-helices. Structural divergence in the common cores is measured by Δ, which varies between 0.62 and 2.31 Å for 32 homologous pairs. The value of Δ depends on the procedure used to define the common cores. The exponential relationship between sequence identity (H) and Δ is given by Δ = 0.40 e^(1.87H). This relationship arises because proteins accept mutations of surface residues more readily than buried residues. Closely related proteins differ mainly in surface residues, while distantly related proteins differ in both surface and buried residues. The results show that the extent of structural changes is directly related to the extent of sequence differences. The degree of success in predicting the structure of a protein from its sequence using an homologous protein depends on the sequence identity. Proteins with >50% sequence homology have close structural models, while those with 20% homology show large structural differences. However, the active sites of distantly related proteins can have similar geometries due to evolutionary structural changes. The study highlights the importance of sequence identity in predicting protein structure and the role of structural changes in evolution.