Identification of Pockets on Protein Surface to Predict Protein–Ligand Binding Sites

摘要: Proteins perform their biological functions in different cell processes mainly by interacting with other molecules such as proteins, ligands, DNAs and RNAs etc. Not all but only parts of residues proteins are involved interactions. Therefore, identification these on a protein is great importance to understanding functions. In the variety interactions, interactions between ligands have been widely studied protein-ligand docking, virtual screening structure-based drug design There exist number cavities or pocket sites surface where small might bind. often first step ligand-binding site prediction. Many computational algorithms tools developed recent decades predict binding from pockets structures, POCKET (Levitt Banaszak 1992), LIGSITE (Hendlich et al. 1997), CAST (Dundas 2006; Binkowski 2003), LIGSITECS/C (Huang Schroeder 2006), PASS (Brady Stouten 2000), Q-SiteFinder (Laurie Jackson 2005), SURFNET (Laskowski 1995), Fpocket (Le Guilloux 2009), GHECOM (Kawabata 2010), ConCavity (Capra POCASA (Yu PocketPicker (Weisel 2007), SiteHound (Ghersi Sanchez 2009; Hernandez 2009) so on. Some methods described details chapters. Most existing for prediction can be classified into two types: geometry-based energy-based. The further grid-based, sphere-based α-shape-based 2010; Yu 2010). grid based methods, structure projected 3D points categorized types “outside protein”, “inside protein” “near surface” according positions related protein. Then those not inside clustered using some geometry attributes grids at recognized end. LIGSITECS, GHECOM, representatives type. LIGSITEcs, three protein, near solvent. For solvent points, seven-direction scanning applied. All will evaluated SSS (surface-solvent-surface) event it has, if point has more equal than five events, normally locates point. LIGSITEcs explained next section. also firstly projects grid, attribute used this method mathematical morphology. It uses theory morphology define region surface. (Masuya Doi there four basic operations dilation, erosion, opening closing probe site. ConCavity, constructed include well. Each scored structural information evolutional information. end, regions many high-scoring considered sites. approaches, common strategy fulfill spheres layer cutting applied when fulfilling. final that which rich spheres. This kind SURFNET, PASS, PHECOM Go 2007) Approaches α-shape Fpocket. computes triangulations protein’s atoms grouped letting sized ones flow towards neighboring larger one. collection empty triangles. Different CAST, idea α- sphere contacting its boundary containing no atom. identify clusters close together potential contrast 2005) aims find computing interaction energy molecule probe. Q-SiteFinder, layers methyl (―CH3) probes initialized calculate van der Waals probes. groups ranked total Those high ligand similar includes Lennard-Jones electrostatics terms energy. Table 2.1 briefly summarizes category methods.