title: Energy exchange network of inter-residue interactions within a thermally fluctuating protein molecule: A computational study.
abstract: Protein function is regulated not only by the structure but also by physical dynamics and thermal fluctuations. We have developed the computer program, CURrent calculation for proteins (CURP), for the flow analysis of physical quantities within thermally fluctuating protein media. The CURP program was used to calculate the energy flow within the third PDZ domain of the neuronal protein PSD-95, and the results were used to illustrate the energy exchange network of inter-residue interactions based on atomistic molecular dynamics simulations. The removal of the α3 helix is known to decrease ligand affinity by 21-fold without changing the overall protein structure; nevertheless, we demonstrated that the helix constitutes an essential part of the network graph.
authors.affiliation: Graduate School of Science, Division of Material Science, Nagoya University, Furo-cho, Chikusa-ku Nagoya, 464-8602, Japan.
authors.forename: Takakazu
authors.initials: T
authors.lastname: Ishikura
authors.affiliation: Graduate School of Science, Division of Material Science, Nagoya University, Furo-cho, Chikusa-ku Nagoya, 464-8602, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Graduate School of Science, Division of Material Science, Nagoya University, Furo-cho, Chikusa-ku Nagoya, 464-8602, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Hatano
authors.affiliation: Graduate School of Science, Division of Material Science, Nagoya University, Furo-cho, Chikusa-ku Nagoya, 464-8602, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Yamato
mesh_terms: D000818:Animals; D001665:Binding Sites; D000076122:Disks Large Homolog 4 Protein; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D054731:PDZ Domains; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D013816:Thermodynamics
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins
keywords: PDZ domain; allostery; inter-residue energy conductivity; ligand binding; molecular dynamics simulations