CCA-2818 Original Scientific Paper Building-block Computation of Wiener-type Indices for the Virtual Screening of Combinatorial Libraries*

Screening virtual and synthetic combinatorial libraries may facili-tate rapid drug lead discovery by selecting subsets of molecules ac-cording to their similarity or dissimilarity toward specific com-pound collections. Topological indices computed from atomic connectivities or graph distances are increasingly used as structu-ral descriptors in order to maximize the molecular diversity of li-braries or to quantify the drug-like character of compounds. In this paper we present efficient equations for the computation of several distance-based topological indices of a molecular graph from the distance invariants of its subgraphs. These equations offer an ef-fective way to compute for non-weighted molecular graphs the Wiener index, even/odd Wiener index, resistance distance index, Wiener polynomial, and even/odd Wiener polynomial. Using a sim-ple and fast algorithm one can compute these topological indices for very large virtual combinatorial libraries without computing the indices from the atomic scale up for each individual compound – rather only distance-based indices of the building blocks are ne-eded to generate the topological indices of the compound assembled from the building blocks. Key words: virtual combinatorial libraries, drug discovery, topologi-cal indices, Wiener index. * Dedicated to Professor Milan Randi} on the occasion of the 70th birthday