ISSN:
1573-4951
Keywords:
combinatorial chemistry
;
drug design
;
electrostatic potential
;
lipophilicity potential
;
molecular modeling
;
molecular shape
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract In this research we test and compare three possible atom-basedscreening functions used in the heuristic molecular lipophilicity potential(HMLP). Screening function 1 is a power distance-dependent function, b $$_{\text{i}} /\left\| {R_{\text{i}}- r} \right\|^\gamma$$ , screening function 2is an exponential distance-dependent function, biexp(‐ $$\left\| {R_i- r} \right\|/d_0 $$ , and screening function 3 is aweighted distance-dependent function, $${\text{sign}}\left( {b_i } \right){\text{exp}}\xi \left( {\left\| {R_i- r} \right\|/\left| {b_i } \right|} \right)$$ For every screening function, the parameters ( $$\gamma $$ ,d0, and $$\xi $$ are optimized using 41 common organic molecules of 4 types of compounds:aliphatic alcohols, aliphatic carboxylic acids, aliphatic amines, andaliphatic alkanes. The results of calculations show that screening function3 cannot give chemically reasonable results, however, both the powerscreening function and the exponential screening function give chemicallysatisfactory results. There are two notable differences between screeningfunctions 1 and 2. First, the exponential screening function has largervalues in the short distance than the power screening function, thereforemore influence from the nearest neighbors is involved using screeningfunction 2 than screening function 1. Second, the power screening functionhas larger values in the long distance than the exponential screeningfunction, therefore screening function 1 is effected by atoms at longdistance more than screening function 2. For screening function 1, thesuitable range of parameter d0 is 1.5 〈 d0 〈 3.0, and d0 = 2.0 is recommended. HMLP developed in this researchprovides a potential tool for computer-aided three-dimensional drugdesign.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008040309114
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