TY - JOUR
T1 - Advances in theoretical studies on the design of single boron atom compounds
AU - Bello, Martiniano
N1 - Publisher Copyright:
© 2018 Bentham Science Publishers.
PY - 2018
Y1 - 2018
N2 - Background: Single Boron Atom Compounds (SBACs) have been used for drug discovery in disease-associated 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 atom parameters. 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.
AB - Background: Single Boron Atom Compounds (SBACs) have been used for drug discovery in disease-associated 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 atom parameters. 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.
KW - Anionic tetragonal arrangement
KW - Docking calculations
KW - Drug discovery
KW - Dynamics simulations
KW - Molecular recognition
KW - Single boron atom compounds
UR - http://www.scopus.com/inward/record.url?scp=85059494922&partnerID=8YFLogxK
U2 - 10.2174/1381612824666181102142432
DO - 10.2174/1381612824666181102142432
M3 - Artículo de revisión
C2 - 30387389
SN - 1381-6128
VL - 24
SP - 3466
EP - 3475
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
IS - 29
ER -