Structural properties of the glutamate in vacuum and in complex with its receptor were analyzed. The analysis was focused on global properties, attempting to characterize features such as overall flexibility and common trends in the conformation set. The glutamate, as other ligands in complex with the receptor, adopts a spatial conformation that corresponds to one of the possible molecular equilibrium states in physiological conditions. The glutamate forms an extended structure for all cases, but the energy of the glutamate round out form is lower than the extended glutamate form. The results showed the glutamate as a flexible molecule, which can easily adapt to different interacting environments, and it can be considered as an approximation to address why glutamate interacts with a great number of molecules. 1. Introduction The amino acid L-glutamate is considered the main excitatory neurotransmitter in mammals Central Nervous System (CNS) [1, 2]. Most of the CNS synapses use glutamate as a fast neurotransmitter, and at least 60% of the synapses in the human brain are glutamatergic [3]. The glutamate has an important physiological role in many aspects of the normal brain function such as cognition, memory, learning, nervous system development, cellular migration, cellular differentiation, and neural death [4, 5]. After being released from a presynaptic cell, glutamate diffuses across the synaptic cleft and binds to its specific receptors in the cell membrane of a postsynaptic cell. Once across the synaptic cleft, glutamate is recognized by glutamate receptors from a high variety of other molecules. Although the mechanism of molecular recognition has long been considered in a key-keyhole relationship, short-range forces have been considered as the primary cause of such interactions [6]. The glutamate (L-isomer) causes depolarization and excitation of neurons, but it does so by acting on a variety of receptors. The AMPA/kainate receptors respond to the glutamic acid analogues, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainic acid. Other receptors, N-methyl-D-aspartate (NMDA) receptor, also belong to the ion-channel-linked superfamily, and there is a population of metabotropic receptors, as upon activation they simulate a second messenger transduction system [7]. The behavior of different neurotransmitters has been mainly studied using physiological and pharmacological techniques in both vertebrate and invertebrate brains, and recent techniques in molecular biology have clarified the amino acid sequences of their binding sites
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