autoclickchem click chemistry in silicoautoclickchem点击化学在硅片.pdf

AutoClickChem: Click Chemistry in Silico 1 2,3,4 Jacob D. Durrant *, J. Andrew McCammon 1 Department of Chemistry Biochemistry, University of California San Diego, La Jolla, California, United States of America, 2 Department of Chemistry Biochemistry, NSF Center for Theoretical Biological Physics, National Biomedical Computation Resource, University of California San Diego, La Jolla, California, United States of America, 3 Department of Pharmacology, University of California San Diego, La Jolla, California, United States of America, 4 Howard Hughes Medical Institute, University of California San Diego, La Jolla, California, United States of America Abstract Academic researchers and many in industry often lack the financial resources available to scientists working in ‘‘big pharma.’’ High costs include those associated with high-throughput screening and chemical synthesis. In order to address these challenges, many researchers have in part turned to alternate methodologies. Virtual screening, for example, often substitutes for high-throughput screening, and click chemistry ensures that chemical synthesis is fast, cheap, and comparatively easy. Though both in silico screening and click chemistry seek to make drug discovery more feasible, it is not yet routine to couple these two methodologies. We here present a novel computer algorithm, called AutoClickChem, capable of performing many click-chemistry reactions in silico. AutoClickChem can be used to produce large combinatorial libraries of compound models for use in virtual screens. As the compounds of these libraries are constructed according to the reactions of click chemistry, they can be easily synthesized for subsequent testing in biochemical assays. Additionally, in silico mode