Journal of Computer-Aided Molecular Design, 12: 63–79, 1998. KLUWER/ESCOM © 1998 Kluwer Academic Publishers. Printed in Belgium. 63 Classification of auxin plant hormones by interaction property similarity indices Sanja Tomi´ c a,b , Razif R. Gabdoulline a , Biserka Koji´ c-Prodi´ c b & Rebecca C. Wade a,∗ a European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany b Rud − er Boškovi´ c Institute, P.O. Box 1016, HR-10001 Zagreb, Croatia Received 16 May 1997; Accepted 20 August 1997 Key words: auxins, molecular alignment, molecular interaction field, molecular modeling, QSAR, similarity index Summary Although auxins were the first type of plant hormone to be identified, little is known about the molecular mech- anism of this important class of plant hormones. We present a classification of a set of about 50 compounds with measured auxin activities, according to their interaction properties. Four classes of compounds were defined: strongly active, weakly active with weak antiauxin behaviour, inactive and inhibitory. All compounds were mod- eled in two low-energy conformations, ‘P’ and ‘T’, so as to obtain the best match to the ‘planar’ and ‘tilted’ conformations, respectively, of indole 3-acetic acid. Each set of conformers was superimposed separately using several different alignment schemes. Molecular interaction energy fields were computed for each molecule with five different chemical probes and then compared by computing similarity indices. Similarity analysis showed that the classes are on average distinguishable, with better differentiation achieved for the T conformers than the P conformers. This indicates that the T conformation might be the active one. Further, a screening was developed which could distinguish compounds with auxin activity from inactive compounds and most antiauxins using the T conformers. The classifications rationalize ambiguities in activity data found in the literature and should be of value in predicting the activities of new plant growth substances and herbicides. Introduction Plant hormones, also known as phytohormones or plant growth substances, are naturally occurring sub- stances which, in low concentrations, influence plant physiology. The term plant growth regulators, al- though also used for plant hormones, encompasses all compounds, natural and synthetic, which when ap- plied to plants evoke a specific physiological response. Of the five groups of plant hormones, the auxins are dealt with in the present analysis. Auxins promote cell enlargement and division, apical dominance, root initi- ation, differentiation of vascular tissue, signaling, and other activities [1]. However, little is known of their activity at the molecular level [1–5]. They belong to a chemically diverse class of compounds, most of which have an aromatic system such as indole, phenyl or ∗ To whom correspondence should be addressed. naphthalene with a side chain containing a carboxyl group attached. Indole-3-acetic acid (IAA) is the most commonly occurring natural auxin, and is followed by 4-chlorindole-3-acetic acid and phenylacetic acid whose distribution is more restricted [1,2]. There are many synthetic auxins and some of them, e.g. 2,4- dichlorophenoxyacetic acid, are used agriculturally as growth regulators and herbicides. The auxin receptor and auxin binding proteins have been central elements in most hypotheses aiming to explain phytohormone action at a molecular level [1–12]. A number of auxin binding proteins (ABPs) have been detected during an almost two-decade long search for such proteins [1–12 and references therein]. Among them, the maize ABP1, a homodimer of 22- kDa subunits, is the clearest candidate for an auxin receptor [1–12]. This protein is located mainly within the lumen of the endoplasmic reticulum, but an im- portant fraction appears to function on the outside