1P008 Crystal structure of the C-type lectin-like domain of CD72(Protein: Structure,Poster,The 52th Annual Meeting of the Biophysical Society of Japan(BSJ2014))

Abstract

As a protein-protein complex structure prediction method, we have developed a procedure to combine recently developed two approaches. The first one is a clustering and reranking method named CyClus which performs a fast clustering using a cylindrical approximation of interface and improves results of rigid-body docking. The second one is free energy evaluation through molecular dynamics simulation using the solution theory in the energy representation. Using this method we can calculate binding free energy differences of generated complex models. The clustering using CyClus efficiently reduces the number of candidates to be evaluated and the free energy analysis serves to accurate evaluation. 1P008B 細胞共受容体 CD72 の C 型レクチン様ドメインの X 線結 晶構造解析 The structure of alpha-synuclein (α-syn) in solution resembles that of a random coil. But, alpha-synuclein is of great interest to Parkinson's researchers because it is a major constituent of Lewy bodies. Here, we try to observe the structural fluctuations of alpha-synuclein and its mutants (WT, A53T, and E46K) by using Diffracted X-ray Tracking (DXT) as xray single molecule observations. In DXT, we observed Brownian motions of his-tagged alpha-synucleins, which are adsorbed on the substrate's surface. DXT experiments used the energy of quasi-white x-rays (energy peak-width of 2% using undulator radiations, 10-20 KeV, BL40XU, SPring-8). From DXT data, we discovered that these alpha-synuclein's dynamic states (structural fluctuation=0.1-0.2 nm) had a clear difference. Molecular docking explores the binding modes of two interacting molecules. The technique is increasingly popular for studying proteinligand interactions and for drug design. A fundamental problem with molecular docking is that orientation space is very large and grows combinatorially with the number of degrees of freedom of the interacting molecules. Here, we describe and evaluate algorithms that improve the efficiency and accuracy of a shape-based docking method. We adopt the molecular organization and sampling techniques to remove the exponential time dependence on molecular size in docking calculations. The possible structures and binding energies in the dissociation process are discussed by using the developed docking program.