title: Role of side-chain interactions on the formation of α-helices in model peptides.
abstract: The role played by side-chain interactions on the formation of α-helices is studied using extensive all-atom molecular dynamics simulations of polyalanine-like peptides in explicit TIP4P water. The peptide is described by the OPLS-AA force field except for the Lennard-Jones interaction between Cβ-Cβ atoms, which is modified systematically. We identify values of the Lennard-Jones parameter that promote α-helix formation. To rationalize these results, potentials of mean force (PMF) between methane-like molecules that mimic side chains in our polyalanine-like peptides are computed. These PMF exhibit a complex distance dependence where global and local minima are separated by an energy barrier. We show that α-helix propensity correlates with values of these PMF at distances corresponding to Cβ-Cβ of i-i+3 and other nearest neighbors in the α-helix. In particular, the set of Lennard-Jones parameters that promote α-helices is characterized by PMF that exhibit a global minimum at distances corresponding to i-i+3 neighbors in α-helices. Implications of these results are discussed.
authors: New Jersey Institute of Technology, Physics Department, University Heights, Newark, New Jersey, 07102-1982, USA.
authors: Farbod
authors: F
authors: Mahmoudinobar
authors: New Jersey Institute of Technology, Physics Department, University Heights, Newark, New Jersey, 07102-1982, USA.
authors: Cristiano L
authors: CL
authors: Dias
authors: Department of Organic Chemistry I and POLYMAT, University of the Basque Country UPV/EHU, Avenida de Tolosa 72, 20018, San Sebastian, Spain IKERBASQUE, Basque Foundation for Science, Maria Diaz de Haro 3, 48013 Bilbao, Spain.
authors: Ronen
authors: R
authors: Zangi
mesh_terms: D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D014867:Water / Q000737:chemistry
chemical_list: D010455:Peptides; D014867:Water; C019529:polyalanine