We developed a new in silico screening method, which is a structure-based virtual fragment screening with protein-compound docking. The structure-based in silico screening of small fragments is known to be difficult due to poor surface complementarity between protein surfaces and small compound (fragment) surfaces. In our method, several side chains were attached to the fragment in question to generate a set of replica molecules of different sizes. This chemical modification enabled us to select potentially active fragments more easily than basing the selection on the original form of the fragment. In addition, the Coulombic and hydrogen bonding interactions were ignored in the docking simulation to reduce the variety of chemical modifications. Namely, we focused on the sizes and the shapes of the side chains and could ignore the atomic charges and types of elements. This procedure was validated in the screenings of inhibitors of six target proteins using known active compounds, and the results revealed that our procedure was effective.