title: Pocket-based drug design: exploring pocket space.
abstract: The identification and application of druggable pockets of targets play a key role in in silico drug design, which is a fundamental step in structure-based drug design. Herein, some recent progresses and developments of the computational analysis of pockets have been covered. Also, the pockets at the protein-protein interfaces (PPI) have been considered to further explore the pocket space for drug discovery. We have presented two case studies targeting the kinetic pockets generated by normal mode analysis and molecular dynamics method, respectively, in which we focus upon incorporating the pocket flexibility into the two-dimensional virtual screening with both affinity and specificity. We applied the specificity and affinity (SPA) score to quantitatively estimate affinity and evaluate specificity using the intrinsic specificity ratio (ISR) as a quantitative criterion. In one of two cases, we also included some applications of pockets located at the dimer interfaces to emphasize the role of PPI in drug discovery. This review will attempt to summarize the current status of this pocket issue and will present some prospective avenues of further inquiry.
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, Jilin, 130022, People's Republic of China.
authors.forename: Xiliang
authors.initials: X
authors.lastname: Zheng
authors.forename: Linfeng
authors.initials: L
authors.lastname: Gan
authors.forename: Erkang
authors.initials: E
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000495:Allosteric Site; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D018631:ras Proteins / Q000737:chemistry*; D019061:src-Family Kinases / Q000737:chemistry*
chemical_list: D000255:Adenosine Triphosphate; D019061:src-Family Kinases; D018631:ras Proteins