Heuristic molecular lipophilicity potential (HMLP) was applied to the study of lipophilicity and hydrophilicity of 20 natural aminoacid side chains. The HMLP parameters, surface area A_i, lipophilic indices L_i and hydrophilic indices H_i of aminoacid side chains were derived from lipophilicity potential L(r). The parameters were correlated with the experimental data of phase transfer free energies of vapor-to-water, vapor-to-octanol, and octanol-to-water through a linear free energy equation ΔG_sol,i^θ＝b₀＋b₁L_i＋b₂H_i＋b₃S_i^＋＋b₄S_i^－. For all above 3 types of transfer free energies between different medium phases, the HMLP parameters of 20 aminoacid side chains provided good descriptions. HMLP is an ab initio quantum chemical approach and a structure-based technique. Except for atomic van der Waals radii, there was no other empirical parameter used. The computational results of HMLP have clear physical and chemical meaning and could provide useful lipophilic and hydrophilic parameters for the studies of proteins and peptides.

Key words: heuristic molecular lipophilicity potential (HMLP), lipophilicity index, protein, aminoacid, biological informatics