SEMINAR

Computational Analysis on Electrostatic Properties of Protein and Protein-Protein Interaction

Abstract
Electrostatic properties of proteins govern most of the biological phenomena, in particular, specific molecular recognitions on protein interfaces, which controls biological signal transductions through protein-protein interactions (PPIs) [1-3]. Appropriate treatment of the electrostatic interaction is critical for computational analyses of PPI in a realistic manner. Since the potential function is long-ranged, it is not simple to handle the interactions in an effective manner: high accuracy, low computational cost, ease of the implementation, and freedom from artifacts.

We have recently developed a novel algorithm, zero-multipole summation method, for evaluating the electrostatic energy of charged particle systems [4-7]. Its simple pair wise form enables us to effectively apply the scheme to high-performance parallel computation with GPGPU systems [8]. Several applications to homogeneous and inhomogeneous molecular systems have confirmed that it could replace the conventional Ewald method in order to perform rapid and accurate molecular dynamics simulations [9-13]. This method is applied to simulate a protein-protein docking procedure in an ab-initio manner based on the computed free energy landscape [14, 15].

References
[1] Nakamura H (1996) Roles of electrostatic interaction in proteins. Quart. Rev. Biophys. 29, 1-90.
[2] Kanamori E et al. (2013) "Biomolecular Forms and Functions" (Eds. Bansal M & Srinivasan N), pp. 160-172, World Scientific Publishing.
[3] Murakami Y et al. (2013) Exhaustive comparison and classification of ligand-binding surfaces in proteins. Protein Science 22, 1379-1391.
[4] Fukuda I et al. (2011) Molecular dynamics scheme for precise estimation of electrostatic interaction via zero-dipole summation principle. J. Chem. Phys., 134, 164107.
[5] Fukuda I, Nakamura H (2012) Non-Ewald methods: Theory and Applications to Molecular Systems. Biophysical Reviews 4, 161-170.
[6] Fukuda I (2013) Zero-multipole summation method for efficiently estimating electrostatic interactions in molecular system. J. Chem. Phys. 139, 174107.
[7] Fukuda I et al. (2014) The Zero-multipole summation method for estimating electrostatic interactions in molecular dynamics: analysis of the accuracy and application to liquid systems. J. Chem. Phys. 140, 194307.
[8] Mashimo T et al. (2013) Molecular Dynamics Simulations Accelerated by GPU for Biological Macromolecules with a Non-Ewald Scheme for Electrostatic Interactions. J. Chem. Theory Comput. 9, 5599-5609.
[9] Fukuda I et al. (2012) Simple and Accurate Scheme to Compute Electrostatic Interactions: Zero-dipole Summation Technique for Molecular System and Application to Bulk Water., J. Chem. Phys. 137, 054314.
[10] Kamiya N et al. (2013) Application of zero-dipole summation method to molecular dynamics simulations of a membrane protein system. Chem. Phys. Lett. 568-569, 26-32.
[11] Arakawa T et al. (2013) Molecular dynamics simulations of a double-stranded DNA in an explicit solvent model with zero-dipole summation method. PLoS ONE 8, e76606.
[12] Kasahara K et al. (2014) A Novel Approach of Dynamic Cross Correlation Analysis on Molecular Dynamics Simulations and its Application to Ets1 dimer–DNA Complex. PLoS ONE 9, e112419.
[13] Nishikawa Y et al. (2014) Structure of the entire stalk region of the dynein motor domain. J. Mol. Biol. 426, 3232–3245.
[14] Higo J et al. (2013) A virtual-system coupled multicanonical molecular dynamics simulation: Principles and applications to free-energy landscape of protein–protein interaction with an all-atom model in explicit solvent. J. Chem. Phys. 138, 184106.
[15] Higo J et al. (2015) Virtual-system coupled adaptive umbrella sampling to compute free-energy landscape for flexible molecular docking. J. Comput. Chem. 36, 1489-1501.

BIOGRAPHY

April 2014 - present, Director of IPR.
April 1999 - present, Professor, Laboratory of Protein Informatics, Institute for Protein Research (IPR), Osaka University
June 2001 - present, Head of PDBj
April 2012 - March 2014, Advisor to Osaka University Trustees
April 1996 - March 1999, Biomolecular Engineering Research Institute, Osaka
August 1987 - March 1996, Protein Engineering Research Institute, Osaka
April 1980 - July 1987, Research Associate at Department of Applied Physics, Faculty of Engineering, the University of Tokyo

Research Fields and Interests:
Structural bioinformatics, biophysical studies about protein architecture, electrostatic properties and enzymatic functions, protein modeling, protein design, structure guided drug development, and molecular and electronic simulation.
Associate Editor of BREV (Biophysical Reviews), and an editorial board member of PEDS (Protein Engineering Design and Selection), J. Struct. Funct. Genomics, Biophysics, and Curr. Opin. Struct. Biol.

Selected Publications:
Kamiya N., Fukuda I., Nakamura H., Application of zero-dipole summation method to molecular dynamics simulations of amembrane protein system. (2013) Chem. Phys. Lett. 568-569, 26-32 (Editor's Choice).
Kinjo A. R., Suzuki H., Yamashita R., Ikegawa Y., Kudou T., Igarashi R., Kengaku Y., Cho H., Standley D. M., Nakagawa A., Nakamura H., Protein Data Bank Japan (PDBj): maintaining a structural data archive and resource description framework format. (2012) Nucleic Acids Research 40, D453-D460.
Patil A., Nakamura H., Disordered domains and high surface charge confer hubs with the ability to interact with multiple proteins in interaction networks. (2006) FEBS Lett. 580, 2041-2045.
Kamiya N, Higo J, Nakamura H., Conformational transition states of beta-hairpin peptide between the ordered and disordered conformations in explicit water. (2003) Protein Science 11, 2297-2307.
Shirai, H., Kidera, A., Nakamura H., H3-rules: Identification of CDR-H3 structures in antibodies. (1999) FEBS Lett. 455, 188-197.