207
Chapter 7
Density Functional Theory Calculations
of Enzyme–Inhibitor Interactions in Medicinal
Chemistry and Drug Design
Alexander B. Rozhenko
© Springer Science+Business Media Dordrecht 2014
L. Gorb et al. (eds.), Application of Computational Techniques in Pharmacy and Medicine,
Challenges and Advances in Computational Chemistry and Physics 17,
DOI 10.1007/978-94-017-9257-8_7
A. B. Rozhenko ()
Institute of Organic Chemistry, National Academy of Sciences of Ukraine,
Murmans’ka str. 5, Kyiv 02660, Ukraine
e-mail: a_rozhenko@ukr.net
Abstract The density functional theory (DFT) is currently predominating theoretical approach in quantum chemistry. It is suitable for investigating structures up to
several hundreds of atoms, studying of reaction pathways and calculating precisely
reaction energy values. The usage of the DFT approach for studying enzyme–substrate interactions could be a prospective way for elaborating new efficient enzyme
inhibitors. This is a direct way to discovery of new drugs and modification of the
existing drugs. While enzymes are still too large for the computational analysis
using DFT, numerous efforts have been exerted in the last years in this field using
simplified enzyme models or calculating for the substrate some valuable properties, important in the enzyme–substrate interactions. These examples have been
analyzed in the current review. A rapid development of new efficient calculation
routines makes it possible to increase the role of the DFT methods in medicinal
chemistry in the nearest future.
Listing of Used Acronyms
ACE
angiotensin-converting enzyme
AChE
acetylcholinesterase
AD
Alzheimer’s disease
AIDS
acquired immune deficiency syndrome
BACE-1 betasite of APP-cleaving enzyme-1
BChE
butyrylcholinesterase
Cat B
cathepsin B
DFT
density functional theory
DNA
deoxyribonucleic acid
EP
electrostatic potential
Chapter 7
Density Functional Theory Calculations
of Enzyme–Inhibitor Interactions in Medicinal
Chemistry and Drug Design
Alexander B. Rozhenko
© Springer Science+Business Media Dordrecht 2014
L. Gorb et al. (eds.), Application of Computational Techniques in Pharmacy and Medicine,
Challenges and Advances in Computational Chemistry and Physics 17,
DOI 10.1007/978-94-017-9257-8_7
A. B. Rozhenko ()
Institute of Organic Chemistry, National Academy of Sciences of Ukraine,
Murmans’ka str. 5, Kyiv 02660, Ukraine
e-mail: a_rozhenko@ukr.net
Abstract The density functional theory (DFT) is currently predominating theoretical approach in quantum chemistry. It is suitable for investigating structures up to
several hundreds of atoms, studying of reaction pathways and calculating precisely
reaction energy values. The usage of the DFT approach for studying enzyme–substrate interactions could be a prospective way for elaborating new efficient enzyme
inhibitors. This is a direct way to discovery of new drugs and modification of the
existing drugs. While enzymes are still too large for the computational analysis
using DFT, numerous efforts have been exerted in the last years in this field using
simplified enzyme models or calculating for the substrate some valuable properties, important in the enzyme–substrate interactions. These examples have been
analyzed in the current review. A rapid development of new efficient calculation
routines makes it possible to increase the role of the DFT methods in medicinal
chemistry in the nearest future.
Listing of Used Acronyms
ACE
angiotensin-converting enzyme
AChE
acetylcholinesterase
AD
Alzheimer’s disease
AIDS
acquired immune deficiency syndrome
BACE-1 betasite of APP-cleaving enzyme-1
BChE
butyrylcholinesterase
Cat B
cathepsin B
DFT
density functional theory
DNA
deoxyribonucleic acid
EP
electrostatic potential