title: Structure-based, biophysical annotation of molecular coevolution of acetylcholinesterase.
abstract: Acetylcholinesterase (AChE) is an important enzyme in the nervous system. It terminates signal transmission at chemical synapses by degrading the neurotransmitter acetylcholine and was found to play a role in plaque formation in Alzheimer's disease. Several functional parts of its structure have been identified in the past. Here, we use a coarse-grained anisotropic network model approach based on structure data to analyze protein mechanics of AChE. Single contacts in the protein are "switched off" and the change in the intrinsic dynamics is measured. We correlate the gained insight with information about coevolution within the molecule derived from multiple sequence alignments. More than 300 AChE sequences were aligned and the mutual information of the positions was calculated. From these structural, biophysical, and evolutionary data we could reveal sites of coevolutionary signatures in AChE, annotate them by the selective pressure induced for biophysical reasons, and further pave the way for a more detailed understanding of evolutionary boundary conditions for AChE.
authors: Bioinformatics & Theoretical Biology, Department of Biology, Technische Universität Darmstadt, 64287 Darmstadt, Germany.
authors: Stephanie
authors: S
authors: Weissgraeber
authors: Franziska
authors: F
authors: Hoffgaard
authors: Kay
authors: K
authors: Hamacher
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D016880:Anisotropy; D055592:Biophysical Phenomena; D019143:Evolution, Molecular; D056004:Molecular Dynamics Simulation; D058977:Molecular Sequence Annotation / Q000379:methods*; D016415:Sequence Alignment
chemical_list: D000110:Acetylcholinesterase