Identification of new, well-populated amino-acid sidechain rotamers involving hydroxyl-hydrogen atoms and sulfhydryl-hydrogen atoms

We identify new, well-populated rotamers that involve the hydroxyl-hydrogen atoms of Ser, Thr and Tyr, and the sulfhydryl-hydrogen atom of Cys, using high-resolution crystal structures (<1.2 ？). Although there were refinement artifacts in these structures, comparison with the electron-density maps allowed the placement of hydrogen atoms involved in hydrogen bonds. The χ2 rotamers in Ser, Thr and Cys are consistent with tetrahedral bonding, while the χ3 rotamers in Tyr are consistent with trigonal-planar bonding. Similar rotamers are found in hydrogen atoms that were computationally placed with the Reduce program from the Richardson lab.Knowledge of these new rotamers will improve the evaluation of hydrogen-bonding networks in protein structures.One important conformational parameter of a protein structure is the sidechain χ torsion angle [1]. In crystal structures, these torsion angles were found to be rotameric [2]: they cluster around specific values, values that can be explained in terms of relatively simple stereo-chemical considerations [3,4]. Consequently, libraries of sidechain rotamers have been compiled [5,6]. These libraries have proven useful in parameterizing sidechain conformations for homology modeling [7], monte-carlo simulations [8], and protein design [9]. Rotamer libraries are also used to build and verify crystallographic models [10]. Although the sidechain rotamers have been extensively studied, there remain a number of rotamers involving hydrogen atoms that have been overlooked.Due to the difficulty in placing hydrogen atoms in protein electron density maps, it has long been customary to omit hydrogen atoms in reporting the crystal structure of a protein. However, Richardson and co-workers showed that positions of hydrogen atoms in high-resolution crystal structures can be confidently projected from the topology of the heavy atoms [11]. The projected hydrogen atoms, in most cases, form better van-der-Waals contacts with the neighboring atoms tha