penicillin (shown in a ball-and-stick form) is shown bound to its target, the transpeptidase from the bacteria streptomyces r61 (the protein is shown as a ribbon diagram). antibiotic drug design is facilitated when an enzyme that is essential to the pathogen's survival is absent or very different in humans. humans do not make peptidoglycan, therefore antibiotics that inhibit this process are selectively toxic to bacteria. selective toxicity is also produced in antibiotics by exploiting differences in the structure of the ribosomes in bacteria, or how they make fatty acids. antivirals drugs that inhibit enzymes needed for the replication of viruses are effective in treating viral infections. antiviral drugs include protease inhibitors used to treat hiv/aids and hepatitis c, reverse-transcriptase inhibitors targeting hiv/aids, neuraminidase inhibitors targeting influenza, and terminase inhibitors targeting human cytomegalovirus. pesticides many pesticides are enzyme inhibitors. acetylcholinesterase (ache) is an enzyme found in animals, from insects to humans. it is essential to nerve cell function through its mechanism of breaking down the neurotransmitter acetylcholine into its constituents, acetate and choline. this is somewhat unusual among neurotransmitters as most, including serotonin, dopamine, and norepinephrine, are absorbed from the synaptic cleft rather than cleaved. a large number of ache inhibitors are used in both medicine and agriculture. reversible competitive inhibitors, such as edrophonium, physostigmine, and neostigmine, are used in the treatment of myasthenia gravis and in anaesthesia to reverse muscle blockade. the carbamate pesticides are also examples of reversible ache inhibitors. the organophosphate pesticides such as malathion, parathion, and chlorpyrifos irreversibly inhibit acetylcholinesterase. herbicides the herbicide glyphosate is an inhibitor of 3-phosphoshikimate 1-carboxyvinyltransferase, other herbicides, such as the sulfonylureas inhibit the enzyme acetolactate synthase. both enzymes are needed for plants to make branched-chain amino acids. many other enzymes are inhibited by herbicides, including enzymes needed for the biosynthesis of lipids and carotenoids and the processes of photosynthesis and oxidative phosphorylation. discovery and design robots are used for the high-throughput screening of chemical libraries to discover new enzyme inhibitors. new drugs are the products of a long drug development process, the first step of which is often the discovery of a new enzyme inhibitor. there are two principle approaches of discovering these inhibitors. the first general method is rational drug design based on mimicking the transition state of the chemical reaction catalysed by the enzyme. the designed inhibitor often closely resembles the substrate, except that the portion of the substrate that undergoes chemical reaction is replaced a chemically stable functional group that resembles the transition state. since the enzyme has evolved to stabilise the transition state, transition state analogues generally possess higher affinity for the enzyme compared to the substrate, and therefore are effective inhibitors. the second way of discovering new enzyme inhibitors is high-throughput screening of large libraries of structurally diverse compounds to identify hit molecules that bind to the enzyme. this method has been extended to include virtual screening of databases of diverse molecules using computers, which are then followed by experimental confirmation of binding of the virtual screening hits. complementary approaches that can provide new starting points for inhibitors include fragment-based lead discovery and dna encoded chemical libraries (del). hits from any of the above approaches can be optimised to high affinity binders that efficiently inhibit the enzyme. computer-based methods for predicting the binding orientation and affinity of an inhibitor for an enzyme such as molecular docking and molecular mechanics can be used to assist in the optimisation process. new inhibitors are used to obtain crystallographic structures of the enzyme in an inhibitor/enzyme complex to show how the molecule is binding to the active site, allowing changes to be made to the inhibitor to optimise binding in a process known as structure-based drug design.: 66 this test and improve cycle is repeated until a sufficiently potent inhibitor is produced.