Library-based lead compound discovery for CS-1 protein in multiple myeloma: homology modelling, molecular dynamic simulations, virtual screening and molecular docking

Abstract

ABSTRACT The signaling lymphocytic activation molecule F7 (CS-1) enables the selective killing of the myeloma cells with minimal side effects on the healthy tissue. In this study, we have modelled the 3D structure of CS-1 followed by performing molecular dynamic simulations. To develop a potential CS-1 modulator, a virtual screening of the ‘Bioactive Compound Database’ was conducted. The screening results have given three interacting regions. The best representative structure of each class and mode of action were revealed. Our study suggests compounds ICG-001, Avanafil, and BPTES, as novel drug candidates at the CS-1 protein target. The molecular dynamic simulation study reveals that the resulted compounds provide different binding patterns over the CS-1 Ig-like V-type domain in which Avanafil and BPTES provide stable interactions with their binding environment located at the bc-hi loops clefts and bc-fg loops clefts, respectively. In contrast, compound ICG-001 shows more flexible and transient non-binding interaction due to the vast binding region over β-sheet strands consisting of H, C and D during the simulation timeline. We conclude that the identified compounds seem to be the best candidates to design a series of new compounds with the ability to bind to CS-1 with potential binding activity to its target.