Table 4. General comparison of the evolution of molecular surface properties with the probe radius, calculated at atom- and amino acid level.

Property (definition)	Atomic property relationship vs. probe radius (R) increase	Atomic property ratio to amino acid homologue
Overall hydrophobicity
Relative density1,2: Overall hydrophobicity/Molecular surface area	Slight increase for most proteins Large increase (from ∼0.02 to ∼0.08 kcal nm−2) for 1AO63 [Figure 3 top]	Generally larger (up to 2.5x); Generally increase for R = 1 to 5 Å, then constant [Figure 3 bottom]
Hydrophilicity
Relative area: Hydrophilic area Total molecular area	Constant, i.e., ∼40% of the total area (1AFU, 1Y4F) or increase from 40% to 50% (1Y4F), 60% (1LYZ) and 80% (1AO6) [Figure 4 top]	Generally smaller, between 40% to 80% Constant (40%, 1Y4F, 1AFU), or increase from 50% up to 80% [Figure 4 bottom]
Relative density: Total hydrophilicity Molecular surface area	Slight increase for most proteins Large increase (from ∼0.02 to ∼0.08 kcal nm−2) for 1AO6 [Figure 5 top]	Generally larger –1.5 to 2.5x Generally constant with R [Figure 5 bottom]
Specific density: Total hydrophilicity Hydrophilic area	Rather constant or a slight decrease (1LYZ) [Figure 6 top]	Much larger, i.e., 2.5–5.5x; Slight decrease with R [Figure 6 bottom]
Hydrophobicity
Relative area: Hydrophobic area Total molecular area	Constant, i.e., ∼40% of the total area (1AFU, 1Y4F) or decrease from 60% to 50% (1Y4F), 40% (1LYZ) and 20% (1AO6) [Figure 7 top]	Much larger, between 2.5x to 17x Constant (1HZH) or increase with R [Figure 7 bottom]
Relative density: Total hydrophobicity Molecular surface area	Slight decrease4 from −0.015 to −0.01 kcal nm−2 (1HZH, 1AFU, 1Y4F). Large decrease, from ∼0.015 to ∼0.005 kcal nm−2 (1AO6, 1LYZ) [Figure 8 top]	Much larger 5 to 20x Generally constant with R [Figure 8 bottom]
Specific density: Total hydrophobicity Hydrophobic area	Decrease from −0.03 and 0.02 to −0.02 and −0.01 kcal nm−2 [Figure 9 top]	Generally larger, i.e., 1–2.5x;Decrease with R [Figure 9 bottom]

Notes:

1. Overall hydrophobicity is the algebraic sum of hydrophilicity (positive sign) and hydrophobicity (negative sign). Consequently, the increase of the overall hydrophobicity means that it is more hydrophilic.

2. The relative density of the overall hydrophobicity is equal to its specific density.

3. PDB codes for model proteins: lysozyme (1LYZ); ribonuclease-A (1AFU); human hemoglobin (1Y4F); human serum albumin (1AO6); human IgG (1HZH).

4. Hydrophobicity is expressed in negative numbers. Consequently, a decrease in hydrophobicity will be represented by a move towards 0.