On the issue of closed versus open forms of gamma-aminobutyric acid (GABA) in water: Ab initio molecular dynamics and metadynamics studies.

Gamma-aminobutyric acid (GABA), a primary neurotransmitter, accomplishes its activities by binding to different receptor sites in different conformations. It is known to have two major conformers: the closed and open forms. Earlier studies on preferred conformation of GABA in water revealed differing results with some reporting the open form while others inferring the closed form to be more stable. We found the existence of many open forms and only one closed form of GABA in water through ab initio metadynamics simulation. Some of the open conformers are equally or more stable while others are less stable than the closed form. Free energy barriers reveal that different conformers are interconvertible at room temperature in typical experimental time scales. Ab initio molecular dynamics simulations are performed to further investigate the inter-conversion of various conformers of GABA in water and their dipole moments and also to make connections to experiments on the conformation of GABA in water.