@article{10.1371/journal.pcbi.1000550, doi = {10.1371/journal.pcbi.1000550}, author = {Hase, Takeshi AND Tanaka, Hiroshi AND Suzuki, Yasuhiro AND Nakagawa, So AND Kitano, Hiroaki}, journal = {PLOS Computational Biology}, publisher = {Public Library of Science}, title = {Structure of Protein Interaction Networks and Their Implications on Drug Design}, year = {2009}, month = {10}, volume = {5}, url = {https://doi.org/10.1371/journal.pcbi.1000550}, pages = {1-9}, abstract = {Protein-protein interaction networks (PINs) are rich sources of information that enable the network properties of biological systems to be understood. A study of the topological and statistical properties of budding yeast and human PINs revealed that they are scale-rich and configured as highly optimized tolerance (HOT) networks that are similar to the router-level topology of the Internet. This is different from claims that such networks are scale-free and configured through simple preferential-attachment processes. Further analysis revealed that there are extensive interconnections among middle-degree nodes that form the backbone of the networks. Degree distributions of essential genes, synthetic lethal genes, synthetic sick genes, and human drug-target genes indicate that there are advantageous drug targets among nodes with middle- to low-degree nodes. Such network properties provide the rationale for combinatorial drugs that target less prominent nodes to increase synergetic efficacy and create fewer side effects.}, number = {10}, }