ci600274f_si_001.pdf (129.44 kB)
An Integrated in Silico Analysis of Drug-Binding to Human Serum Albumin
journal contribution
posted on 2006-11-27, 00:00 authored by Ernesto Estrada, Eugenio Uriarte, Enrique Molina, Yamil Simón-Manso, George W. A. MilneApproaches such as quantitative structure−activity relationships (QSAR) and molecular modeling are
integrated with the study of complex networks to understand drug binding to human serum albumin (HSA).
A robust QSAR model using the topological substructural molecular descriptors/design (TOPS-MODE)
approach has been derived and shows good predictability and interpretability in terms of structural contribution
to drug binding to HSA. A perfect agreement exists between the group/fragment contributions found by
TOPS-MODE and the specific interactions of drugs with HSA. These results indicate a preponderant
contribution of hydrophobic regions of drugs to the specific binding to drug-binding sites 1 and 2 in HSA
and specific roles of polar groups which anchor drugs to HSA binding sites. The occurrence of fragments
contributing to drug binding to HSA can be represented by complex networks. The fragment-to-fragment
complex network displays “small-world” and “scale-free” characteristics and in this way is similar to other
complex networks including biological, social, and technological networks. A small number of fragments
appear very frequently in most drugs. These molecular “empathic” fragments are good candidates for guiding
future drug discovery research.