Abstract: In this research the structure-based method, heuristic molecular lipophilicity-hydrophilicity potential (HMLP), describing of molecular lipophilicity and hydrophilicity potential on molecular surfaces was introduced. The ESP (electrostatic potential) V(r) on molecular van der Waals surface is calculated, then molecular lipophilicity potential L(r) is constructed by comparing the polarity with the ESP on the surrounding atoms through a screening function. HMLP can be used to describe the molecular interactions with polar and non-polar solvent molecules taking the advantage of the polarity of HMLP. Therefore, HMLP is a unified lipophilicity and hydrophilicity potential, its positive values represent lipophilicity and negative values represent hydrophilicity. Several examples given in this paper show that HMLP gives a better descriptions for ligand-receptor interaction than other methods, such as atomic partial charges and empirical lipophilicity potential. After parameterization and indexing, hopefully, HMLP may be applied to the studies of function and structure of proteins and the genomic decoding of DNA and RNA.

Key words: Lipophilicity-hydrophilicity potential(HMLP), Molecular simulation, Bioinformatics, Design of drug molecule, Quantum chemistry