Ab initio molecular dynamics free-energy study of microhydration effects on the neutral-zwitterion equilibrium of phenylalanine.
The structures and relative energies of the most stable conformers of both naked and microsolvated phenylalanine, Phe.(H(2)O)(n)(n=0-3), are calculated by density functional theory. For selected structures, coordination-constrained ab initio molecular dynamics simulations determine the proton-transfer mechanism connecting neutral and zwitterionic forms of Phe. The associated free-energy profiles are calculated by thermodynamic integration. While no zwitterionic free-energy minimum is found for naked Phe, microsolvation is found to stabilize the zwitterionic form. For cluster sizes n > or = 3, the proton-transfer equilibrium shifts towards the zwitterionic structure for specific proton-transfer pathways. The energetically most favourable interconversion path between the neutral and zwitterionic forms is through a H(2)O bridge with free-energy barriers as low as 14.4 kJ mol(-1) for Phe.(H(2)O)(3). The free energy required for breaking a carboxylic OH bond involved in intramolecular hydrogen bonding is typically lower than in the water-assisted case. However, the resulting zwitterion turns out to be unstable with respect to the backward proton-transfer reaction.
Lehrstuhl für Theoretische Chemie, Ruhr-Universität Bochum, 44780, Bochum, Germany.
Pawel
P
Rodziewicz
Nikos L
NL
Doltsinis
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D008958:Models, Molecular; D008968:Molecular Conformation; D010649:Phenylalanine / Q000737:chemistry*; D011522:Protons; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D011522:Protons; D014867:Water; D010649:Phenylalanine