Frequent side chain methyl carbon-oxygen hydrogen bonding in proteins revealed by computational and stereochemical analysis of neutron structures.
The propensity of backbone Cα atoms to engage in carbon-oxygen (CH · · · O) hydrogen bonding is well-appreciated in protein structure, but side chain CH · · · O hydrogen bonding remains largely uncharacterized. The extent to which side chain methyl groups in proteins participate in CH · · · O hydrogen bonding is examined through a survey of neutron crystal structures, quantum chemistry calculations, and molecular dynamics simulations. Using these approaches, methyl groups were observed to form stabilizing CH · · · O hydrogen bonds within protein structure that are maintained through protein dynamics and participate in correlated motion. Collectively, these findings illustrate that side chain methyl CH · · · O hydrogen bonding contributes to the energetics of protein structure and folding.
Departments of Biophysics and Molecular, Cellular, University of Michigan, Ann Arbor, MI 48109, USA.|Departments of Biochemistry & Physics, Stanford University, Stanford, CA 94305.
Joseph D
JD
Yesselman
Departments of Biophysics and Molecular, Cellular, University of Michigan, Ann Arbor, MI 48109, USA.|Department of Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.|Department of Biological Chemistry, Howard Hughes Medical Institute, University of Michigan, Ann Arbor MI 48109 USA.
Scott
S
Horowitz
Departments of Biophysics and Molecular, Cellular, University of Michigan, Ann Arbor, MI 48109, USA.|Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Charles L
CL
Brooks
Department of Biological Chemistry, Howard Hughes Medical Institute, University of Michigan, Ann Arbor MI 48109 USA.
Raymond C
RC
Trievel
D002244:Carbon / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D009502:Neutrons; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013237:Stereoisomerism
D011506:Proteins; D002244:Carbon; D010100:Oxygen
CH···O; CH···O CH···O; CHO; CH···O; hydrogen bond; molecular dynamics; neutron structure; quantum mechanics