Quantum calculations, structure-activity

PW91 (Perdew, Wang 1991) a gradient corrected DFT method QCI (quadratic conhguration interaction) a correlated ah initio method QMC (quantum Monte Carlo) an explicitly correlated ah initio method QM/MM a technique in which orbital-based calculations and molecular mechanics calculations are combined into one calculation QSAR (quantitative structure-activity relationship) a technique for computing chemical properties, particularly as applied to biological activity QSPR (quantitative structure-property relationship) a technique for computing chemical properties... 

Many computational studies in heterocyclic chemistry deal with proton transfer reactions between different tautomeric structures. Activation energies of these reactions obtained from quantum chemical calculations need further corrections, since tunneling effects may lower the effective barriers considerably. These effects can either be estimated by simple models or computed more precisely via the determination of the transmission coefficients within the framework of variational transition state calculations [92CPC235, 93JA2408]. 

Martin, M., R. Carbo, C. Petrongolo, and J. Tomasi. 1975. Structure-Activity Relationships of Phenylalamine. A Comparison of Quantum Mechanical SCF ab initio and Semiempirical Calculations. J. Am Chem. Soc. 97, 1338. 

Considering the last two paragraphs one encounters an other problem of systematic drug design In order to select appropriate test compounds one needs to know the relevant parameters. These in turn can only be found through structure-activity-analysis based on the selected compounds. In other words, one needs to know the results which are obtained from the test series before this series can be designed properly. How can this problem be solved As in other similar cases (e.g. the calculation of orbital energies in quantum mechanics) an iterative procedure can be applied. Such a procedure is visualized in Scheme 1. 

Gruber, C. and Buh, V. (1989) Quantum mechanically calculated properties for the development of quantitative structure-activity relationships (QSARs). pfCa values of phenols and aromatic and aliphatic carboxylic acids. Chemosphere, 19, 1595-1609. 

Cramer, C. J., G. R. Famini, and A. FI. Lowrey. 1993. Use of calculated quantum chemical properties as surrogates for solvatochromic parameters in structure-activity relationships. Chem. Re 6 599-605. 

Quantum Chemical Descriptors in Structure-Activity Relationships — Calculation, Interpretation,... 

Schuurmann G (2004) Quantum chemical descriptors in structure-activity relationships - calculation, interpretation, and comparison of methods. In Cronin MTD (ed) Predicting chemical toxicity and fate. CRC, Boca Raton FL... 

However, the studies on the calcium channel blockers remained centered even today around the l,4-dihydropyridine class. Since this class of compounds can also act as calcium channel activators, attention has always been drawn towards their structure-activity relationship studies. Attempts were made to differentiate in the mechanisms of their agonist and antagonist activities. On the basis of the force field and quantum mechanical calculations, Holtze and Marrer [51] discovered a imique area of the molecular potentials where Ca agonists and antagonists possess potential of opposite sign. These authors demonstrated that the molecular potential of a simple receptor site was reduced by interaction with calciiun channel activators and, on the contrary, increased by interaction with calcium channel blockers. These opposite effects probably could be the basis for the opposite actions of DHP enantiomers at the potential-dependent calcium channel. 

C. J. Cramer, G. R. Famini, and A. H. Lowrey, Acc. Chem. Res., 26, 599 (1993). Use of Calculated Quantum Chemical Properties as Surrogates for Solvatochromic Parameters in Structure-Activity Relationships. 

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