A QM/MM Hybrid Simulation of 5- Hydroxytryptophan in Solution M. S. AMARAL, 1 M. LOOS, 2 A. S. ITO 3 1 Departamento de Fı ´sica Geral, Instituto de Fı ´sica, Universidade de Sa ˜o Paulo, CP 66318, CEP 05315-970, Sa ˜o Paulo, Brasil 2 Departamento de Quı ´mica Fundamental, Instituto de Quı ´mica, Universidade de Sa ˜o Paulo, CP 26077, CEP 05513-970, Sa ˜o Paulo, Brasil 3 Departamento de Fı ´sica e Matema ´tica, FFCLRP, Universidade de Sa ˜o Paulo, CEP 14040-901, Ribeira ˜o Preto, Brasil Received 17 November 2001; accepted 6 April 2003 DOI 10.1002/qua.10697 ABSTRACT: The 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  1 and  2 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 Key words: 5-hydroxytryptophan; optical absorption spectrum; QM/MM hybrid simulation; SPC/E model Correspondence to: M. S. Amaral; e-mail: msamaral@usp.br Present address: Departamento de Ciencias Exatus, Campus de Corumba ´, Universidade Federal de Mato Grosso do Sul, CP 252, CEP 79304-020, Corumba ´, Brasil. Contract grant sponsors: Fundac ¸a ˜ o de Amparo a ` Pesquisa do Estado de Sa ˜o Paulo; Coordenac ¸a ˜o de Aperfeic ¸oamento de Pes- soal do Ensino Superior; Conselho Nacional de Desenvolvi- mento Cientı ´fico e Tecnolo ´ gico. International Journal of Quantum Chemistry, Vol 95, 289 –294 (2003) © 2003 Wiley Periodicals, Inc.