Molecular structure and dynamics of serotonin

Area of Science:

• Computational chemistry
• Molecular modeling
• Biophysics

Background:

• Serotonin is a crucial neurotransmitter involved in various physiological processes.
• Understanding the conformational flexibility of protonated serotonin is key to elucidating its receptor interactions.
• Previous studies have explored serotonin's structure, but detailed conformational analysis under different conditions is needed.

Purpose of the Study:

• To investigate the electronic structure and low-energy conformations of protonated serotonin.
• To examine the molecule's flexibility and internal motions using molecular dynamics.
• To understand how side chain conformation influences molecular electrostatic potentials and receptor binding.

Main Methods:

• Quantum mechanical and molecular mechanical calculations (AMBER force field).
• Molecular dynamics simulations in vacuo and aqueous solution.
• Ab initio molecular electrostatic potential calculations and atomic charge projection.

Main Results:

• Both gauche and anti conformers were observed in aqueous solution; only gauche conformers in vacuo.
• Molecular dynamics revealed side chain adaptability for receptor binding site fitting.
• Extended side chain conformations exhibited lower phenyl ring electrostatic potentials compared to folded ones.

Conclusions:

• Protonated serotonin exhibits conformational flexibility, with side chain adjustments facilitating receptor interactions.
• The hydroxyl group's influence on electrostatic potentials is conformation-dependent.
• Computational methods provide valuable insights into serotonin's behavior relevant to its biological function.