title: Can proteins and crystals self-catalyze methyl rotations?
abstract: The chi (C(alpha)-C(beta)) torsional barrier in the dipeptide alanine (N-methyl-l-alanyl-N-methylamide) crystal was investigated using ab initio calculations at various levels of theory, molecular mechanics, and molecular dynamics. For one of the two molecules in the asymmetric unit the calculations suggest that rotation around the chi dihedral angle is catalyzed by the crystal environment, reducing by up to approximately 2kT the torsional barrier in the crystal with respect to that in the gas phase. This catalytic effect is present at both low and room temperature and originates from a van der Waals destabilization of the minima in the methyl dihedral potential coming from the nonbonded environment of the side chain. Screening of a subset of the Protein Data Bank with a pharmacophore model reproducing the crystal environment around this side chain methyl identified a protein containing an alanine residue with an environment similar to that in the crystal. Calculations indicate that this chi torsional barrier is also reduced in the protein at low temperature but not at room temperature. This suggests that environment-catalyzed rotation of methyl groups can occur both in the solid phase and in native biological structures, though this effect might be temperature-dependent. The relevance of this catalytic effect is discussed in terms of its natural occurrence and its possible contribution to the low-frequency vibrational modes of molecules.
authors.affiliation: School of Chemical Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. jerome@scs.uiuc.edu
authors.forename: Jerome
authors.initials: J
authors.lastname: Baudry
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Smith
mesh_terms: D002384:Catalysis; D003461:Crystallography / Q000379:methods*; D016208:Databases, Factual; D004151:Dipeptides / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*
chemical_list: D004151:Dipeptides; D011506:Proteins; C002956:alanylalanine