Quantum mechanical (QM) methods such as density functional theory have been consistently shown to be highly accurate in identifying small molecule low-energy conformations. However, QM methods are compute intensive, which tends to limit their wider application, in particular for tasks such as interactive structure-based drug design or virtual screening that requires large number of such calculations on millions of compounds. We are leveraging ORION cloud computing framework (OpenEye Scientific Software, Santa Fe, NM) to perform QM-based dihedral energy scan of a large number of small molecule fragments that span the huge swath of chemical space available in our internal compound collection. In this talk, we will present the results of a systematic analysis of torsion strain observed in small molecule crystal structures and bioactive conformations in protein-ligand complexes. We will discuss other applications of torsion energy profiles to improve virtual screening hit rates and better guide structure-based design.

Leveraging cloud computing for large-scale QM calculations: Application to virtual screening and structure-based design

255th National Meeting (2018)

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