Cea de-a 224-a Consfatuire a Societatii Americane de Chimie va avea loc la Boston, Massacusetts, intre 18 si 22 August 2002. Vizitati situl web al ACS pentru detalii la http://chemistry.org/portal/Chemistry?PID=acsdisplay.html&DOC=meetings\boston2002\index.html

Al 14-lea Simpozion European de QSAR, "Proiectand medicamente - probleme si solutii", va avea loc intre 8 si 13 septembrie 2002, la Bornemouth, UK. Vizitati situl web pentru detalii la http://www.euro-qsar.org/

Aceasta conferinta anuala, organizata de Cambridge Healthtech Institute, are loc la San Diego pe 11-12 februarie 2002. Vezi http://www.healthtech.com/2002/mld/index.htm pentru detalii. Acolo ai ocazia sa ma intilnesti. Includ si rezumatul conferintei pe care o voi prezenta, extras de la pagina web de mai sus (in engleza). 9:20 Increasing Pharmacokinetics Awareness in Early Drug Discovery Dr. Tudor I. Oprea, Associate Director, EST Lead Informatics

VALIDATE is a hybrid approach to predict the binding affinity of novel ligands for receptors of known three-dimensional structure. This approach calcs. physicochem. properties of the ligand and the receptor-ligand complex to est. the free energy of binding. The enthalpy of binding is calcd. by mol. mechanics while properties such as complementary hydrophobic surface area are used to est. the entropy of binding through heuristics. A diverse training

Inhibition of aromatase, a cytochrome P 450 that converts androgens to estrogens, is relevant in the therapeutic control of breast cancer. We investigate this inhibition using a three-dimensional quant. structure-activity relationship (3D QSAR) method known as Comparative Mol. Field Anal., CoMFA [Cramer III, R.D. et al., J. Am. Chem. Soc., 110 (1988) 5959]. We analyzed the data for 50 steroid inhibitors [Numazawa, M. et al., J. Med. Chem., 37 (1994)

Twenty-seven disperse azo dyes were analyzed using Quant. Structure-Activity Relationship (QSAR) methods by correlating variations in the chem. structure with -°, the affinity to cellulose fiber. Classical QSAR results, r2 of 0.32 for CLogP (the calcd. octanol-water partition coeff.) and r2 of 0.924 for MTD (min. topol. difference), suggest that steric, but not hydrophobic, effects are important. For Comparative Mol. Field Anal. (CoMFA), a 3-dimensional

Comparative mol. field anal. (CoMFA), a three-dimensional quant. structure-activity relation (3D-QSAR) paradigm, was used to examine the estrogen receptor (ER) binding affinities of a series of structurally diverse natural, synthetic, and environmental chems. of interest. The CoMFA/3D-QSAR model is statistically robust and internally consistent, and successfully illustrates that the overall steric and electrostatic properties of structurally diverse

A three-dimensional (3D) model for an RNA mol. that selectively binds theophylline but not caffeine is proposed. This RNA, which was found using SELEX (Jension et al., 1994), is 10 000 times more specific for theophylline (KD = 320 nM) than for caffeine (KD = 3.5 mM), although the two ligands are identical except for a Me group substituted at N7 (present only in caffeine). The binding affinity for ten xanthine-based ligands was used to derive a comparative

The all-grid probe Lennard-Jones 6-12 potential, typically used as steric descriptor in CoMFA, has been replaced by the vols. of van der Waals envelopes intersections between the probe-atom and the ligand mols. under investigation. The intersection vols. present a smoother distance dependence that overcomes the problems arising from formulation of a precise alignment and docking into the 3D lattice. A CoMFA-type application on a set of 78 steroid

A review with 76 refs. is given on methods that use the receptor's 3-dimensional structure to derive the scoring function for predicting binding affinities including general comments on scoring functions, the LUDI scoring function, the Wallqvist scoring function, the Verkhivker scoring function, VALIDATE, the Jain scoring function, the HTS approach, and prospects of scoring functions. Enzymes as examples are given.