HINT: a new method of empirical hydrophobic field calculation for CoMFA.
An empirical hydrophobic field-like 3D function has been calculated with the program HINT (hydrophobic interactions) and imported into the SYBYL implementation of CoMFA (Comparative Molecular Field Analysis). The addition of hydrophobicity appears to offer increased chemical interpretability of CoMFA models. An example is given using the steroid model reported by Cramer et al. (J. Am. Chem. Soc., 110 (1988) 5959). While addition of the HINT field did not improve statistical parameters in this model, the CoMFA coefficient contours from the hydrophobic field unambiguously define the most active steroid molecules in the chemical terms of hydrophobic and polar substituents.
Kellogg
G E
GE
Department of Medicinal Chemistry, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0540.
Semus
S F
SF
Abraham
D J
DJ
D000450:Aldosterone / Q000737:chemistry*; D003196:Computer Graphics; D003348:Cortisone / Q000737:chemistry*; D015195:Drug Design; D004958:Estradiol / Q000737:chemistry*; D006854:Hydrocortisone / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D012984:Software; D013329:Structure-Activity Relationship
D000450:Aldosterone; D004958:Estradiol; D003348:Cortisone; D006854:Hydrocortisone