title: Ligand-induced protein responses and mechanical signal propagation described by linear response theories.
abstract: In this study, a general linear response theory (LRT) is formulated to describe time-dependent and -independent protein conformational changes upon CO binding with myoglobin. Using the theory, we are able to monitor protein relaxation in two stages. The slower relaxation is found to occur from 4.4 to 81.2 picoseconds and the time constants characterized for a couple of aromatic residues agree with those observed by UV Resonance Raman (UVRR) spectrometry and time resolved x-ray crystallography. The faster "early responses", triggered as early as 400 femtoseconds, can be best described by the theory when impulse forces are used. The newly formulated theory describes the mechanical propagation following ligand-binding as a function of time, space and types of the perturbation forces. The "disseminators", defined as the residues that propagate signals throughout the molecule the fastest among all the residues in protein when perturbed, are found evolutionarily conserved and the mutations of which have been shown to largely change the CO rebinding kinetics in myoglobin.
authors.affiliation: Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan. Electronic address: lwyang@life.nthu.edu.tw.
authors.forename: Lee-Wei
authors.initials: LW
authors.lastname: Yang
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan. Electronic address: kitao@iam.u-tokyo.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Kitao
authors.affiliation: Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Bang-Chieh
authors.initials: BC
authors.lastname: Huang
authors.affiliation: Quantum Beam Science Directorate, Japan Atomic Energy Research Agency, Kyoto, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Gō
mesh_terms: D001696:Biomechanical Phenomena; D002248:Carbon Monoxide / Q000378:metabolism; D019143:Evolution, Molecular; D007700:Kinetics; D008024:Ligands; D055595:Mechanical Phenomena; D008954:Models, Biological; D008958:Models, Molecular; D009068:Movement; D009154:Mutation; D009211:Myoglobin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D008024:Ligands; D009211:Myoglobin; D002248:Carbon Monoxide