One QSAR pharmacophore model predicted the most favorable amide structure to consist of an aliphatic moiety and an aromatic hydrophobic moiety separated by a highly polar carboxyl group. Another 3D QSAR model defined an optimal structural pattern that consists of two oxygen atoms positioned a certain distance from each other and joined by a lipophilic moiety. Predictive models have also been derived by using multi-linear QSAR based on experimental and theoretical descriptors. Protection times of a large set of carboxamides and N-acylpiperidines were qualitatively analyzed using artificial neural networks and multiple linear regression. One more example is the study of sesquiterpenes occurring in essential oils of plants that possess remarkable insect repellent ability, sometimes comparable in efficacy to DEET. The repellents in this study were classified as early spatial, late spatial, and contact. It was also stressed that a few chemical bond separation between the hydroxyl and the hydrophobic fragments is beneficial for repellent activity. All of the above computational studies were based solely on structural characteristics of odorants. Until very recently, no valid information on putative molecular targets was available. The yellow fever mosquito, Aedes aegypti, has 66 identified odorant binding proteins, while more than 80 OBP encoding genes were found in the Anopheles gambiae genome. Recently published studies of OBP are based on available crystallographic data, biochemical assays, and in silico molecular modeling and docking. For example, ligand affinities of some benzoates and phthalates were experimentally measured for AaegOBP22 using immunofluorescence and fluorescent probe techniques. Interaction of odorants with OBPs and ORs and ORN responses are potentially attractive targets for QSAR analysis: expressed quantitatively they can be used as predictors for repellency or attraction along with theoretical and empirical molecular descriptors of natural and synthetic semiochemicals. OBPs represent the first ��selection gate�� in a multistage odor perception process. Expression, Tasocitinib purification, and crystallization are currently becoming possible for OBPs which has made the tertiary structures of some OBPs available for computer modeling. However, biological systems feasible for efficient, large-scale productions of ORs have been proposed only recently, and partial homology modeling and 
docking studies have been performed so far only for human G protein-coupled ORs. As for the neurophysiological responses, they can be quantified as currents, spike frequencies of a specific ORN, or activity changes within a set of glomeruli of the antennal lobe. The latter, for example, was recently studied along with directed and undirected movement responses for attractive odors in walking Drosophila. The search for more stable and potent repellents that are less toxic to humans and are environmentally benign is of imminent importance. Mosquitoes continue to be vectors that cause diseases such as malaria, West Nile virus, yellow fever, among others of medical and SAR131675 veterinary significance. An ideal repellent needs to be highly effective and long-lasting, while nontoxic for humans and other non-target species. It also has needs user acceptance, implying that it has benign or desirable cosmetic characteristics. Another very important issue is the cost of production and deployment, because much of the malaria threat resides in Africa and many African nations cannot afford expensive vector control tools. An integrated computational approach would be highly relevant in this regard. It can shorten discovery time and lower cost by reduction of the vast resources required for classical trial-and-error methods based on screening of large compound libraries.