Background: Single Boron Atom Compounds (SBACs) have been used for drug discovery in diseaseassociated
proteins due to the empty p-orbital in the atomic structure of boron, which allows it to experience
diverse binding modes during molecular recognition with a range of proteins.
Objective: During the molecular recognition process with a protein target, SBACs can assume an anionic tetragonal
arrangement or a neutral trigonal planar structure to produce four possible reversible covalent or non-covalent
binding modes with a protein. However, the development of new SBACs has been hampered by the fact that most
of the force fields present in many of the software packages used in drug design lack the various types of boron
Methods: We review in silico studies in which a series of theory-based computational strategies have been used
to overcome the lack of boron parameters in most of the force fields used in drug design.
Results: The modeling studies discussed in this review have provided substantial insight into the molecular recognition
of SBACs targeting different receptors, including the elucidation of some of the key interactions, which
serve as a guide for the development of selective SBACs.
Conclusion: Although the strategies employed in many of the studies presented here should serve in the development
of selective SBACs, it is clear that the development of the precise force field parameters, which include
not only the individual atom types but also the entire molecule, is still lacking, yet it is a necessary requirement
for the design of new SBACS as well as for gaining insight into their molecular recognition.