We have been able to show that the three clearly identified atoms comm
on to the inhibitory neurotransmitters glycine and GABA, that we previ
ously hypothesized to serve as attachment points at the glycinergic an
d gabanergic receptor, can indeed interact through both electrostatic
and hydrogen bonding to several amino acids, which have been identifie
d in molecular biological investigations as both present and critical
in the physiological functioning of key polypeptides common to these i
nhibitory receptors, In addition, amino acids also involved in stabili
zing the interaction between the antagonists strychnine and R5135 at t
he glycinergic and gabanergic receptors, respectively, have been shown
to fit our complex model, We identify in detail molecular mechanisms
to explain how glycine and GABA initiate chloride ion movement from ex
traneuronal fluid in the synaptic cleft to intraneuronal volume, In ad
dition, we also identify the molecular mechanisms involved in the bloc
king of chloride ion movement by strychnine at the glycinergic recepto
r and by R5135 at the gabanergic receptor, We also present two compute
r-generated color prints, one for the glycine receptor and one for the
GABA receptor, which show the quantum mechanically geometry optimized
complex formed between receptor side chains, i.e., the part of the am
ino acids in the polypeptide that interacts with the zwitterionic inhi
bitory neurotransmitters, These computer-generated color figures also
show a) the important electrostatic and hydrogen bonding in these inte
ractions, b) a van der Waals model of this complex to illustrate that
no steric repulsions exist, and c) the molecular electrostatic potenti
al energy map showing the electrostatic potentials of neurotransmitter
bound to the receptor model, Finally, we show with computer calculati
ons that the pseudo-rings, formed between the positive quanidinium gro
up in arginine and one of the oxygen atoms in the carboxyl group in bo
th glycine or GABA, result in a positive planar region which appears t
o be involved in a charge-transfer complex with aromatic benzene group
s in amino acids such as phenylalanine and tryosine. (C) 1996 Wiley-Li
ss, Inc.