A QM/MM hybrid simulation of 5‐hydroxytryptophan in solution

Abstract

AbstractThe nonnatural amino acid 5‐hydroxytryptophan (5OHW) has been proposed as a fluorescence probe for protein structure, function, and dynamics studies. Relative to the natural fluorophore, tryptophan, 5OHW has a red‐shifted absorption edge, which permits selective photo excitation of 5OHW in the presence of W residues. In this work, we present results of quantum mechanics/molecular mechanics (QM/MM) hybrid simulation of a 5OHW zwitterionic molecule in a box of water, using the computational package THOR. The 5OHW zwitterion is described quantum chemically, applying the AM1 semiempirical Hamiltonian while the water molecules are treated classically by the extended simple‐point–charge model. The behavior of the dihedral angles χ1 and χ2 is discussed in terms of the exponential fluorescence decay in aqueous solution. Theoretical optical absorption spectra, obtained by INDO/S‐CIS semiempirical method either in vacuum or in the continuum model using an ellipsoidal cavity are discussed and compared with experimental data and recent results of INDO/S‐CIS semiempirical absorption spectra calculated from optimized geometries obtained with ab initio Hartree–Fock 4‐31G in gas phase. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 95: 289–294, 2003