Biocaralysis, zyxwvutsr 1994, zyxwvutsrqp Vol. 9. pp. 221-239 Reprints available directly from the publisher Photocopying permitted by license only 01994 Harwood Academic Publishers GmbH Printed in Malaysia zyx On the Prediction of the Enantioselectivity of Cundidu zy rugusu Lipase by Comparative Molecular Field Analysis. K. Faber, H. Griengl, H. Honig, J. Zuegg* Institute of Organic Chemistry, Graz University of Technology, Stremayrg. 16, A-8010 Graz, Austria Comparative molecular field analysis (CoMFA) was used to derive a quantitative substrate model for the enzymatic resolution of norbomanol esters by the Lipase of Cundidu rugosu. Within these calculations, the steric and electrostatic interactions of both enantiomers and the differences in the corresponding two fields were used for the correlation of the substrate structure with the enantiose- lectivity of the hydrolysis. Different alignments of the molecules were used to improve the model. KEY WORDS Comparative Molecular Field Analysis (CoMFA), lipase, Cundida rugosu, substrate model. INTRODUCTION Over the past few years enzymes zyxwvu - in particular hydrolases - have increasingly been rec- ognized zyxwvut as useful chiral catalysts for the enantioselective transformations of synthetic organic compounds (Poppe and Novak, 1992). Especially lipases have been found to be very versatile by tolerating a wide variety of substrate structures while still retaining their high ability to recognize chirality. To optimize a novel resolution process, it is highly de- sirable to summarize the already available results and to generate a kind of general rule of acceptance and selectivity of a particular enzyme. This would limit a tedious trial and error testing on novel sobstrates, if their structural parameters could apriori be narrowed down to the one with a high probability of successfd conversion and high selectivity (Faber, 1992). There exist approaches to predict the enantioselectivity by calculating the interaction (Fitzpatrick et al., 1992) or the relative position (Ortiz de Montellano et al., 1991) of both enantiomers relative to the enzyme using molecular dynamics methods or by calculating the energy of the transition state of both enantiomers (Norin et al., 1993). But in all cases, 221 Biocatal Biotransformation Downloaded from informahealthcare.com by University of Queensland on 10/01/14 For personal use only.