Hybrid Quantum Mechanical/Molecular Mechanical Methods For Studying Energy Transduction in Biomolecular Machines

Abstract

Hybrid quantum mechanical/molecular mechanical (QM/MM) methods have become indispensable tools for the study of biomolecules. In this article, we briefly review the basic methodological details of QM/MM approaches and discuss their applications to various energy transduction problems in biomolecular machines, such as long-range proton transports, fast electron transfers, and mechanochemical coupling. We highlight the particular importance for these applications of balancing computational efficiency and accuracy. Using several recent examples, we illustrate the value and limitations of QM/MM methodologies for both ground and excited states, as well as strategies for calibrating them in specific applications. We conclude with brief comments on several areas that can benefit from further efforts to make QM/MM analyses more quantitative and applicable to increasingly complex biological problems. Expected final online publication date for the Annual Review of Biophysics, Volume 52 is May 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Comment on “Applicability of perturbed matrix method for charge transfer studies at bio/metallic interfaces: a case of azurin” by O. Kontkanen, D. Biriukov and Z. Futera, Phys. Chem. Chem. Phys., 2023, 25, 12479

“…2) results in higher polarizabilities: a 0 (Bchl) = 41.5 Å 3 and a 0 (Bchl À ) = 41.9 Å 3 . Both numbers are somewhat below the polarizability C60 Å 3 estimated from eqn (11) and about twice lower than direct calculations: a 0 (Bchl) = 85.8 and a 0 (Bchl À ) = 93.6 Å 3 (B3LYP/6-311+g(d)), which are allowed in Gaussian 16 40 through fitting of the ground-state energy in the presence of the field 41 to the quadratic functionality in eqn (1).…”

“…It displaces the electronic energies by the energy of Coulomb interaction of the quantum-mechanical (QM) region with the surrounding medium, E C = 〈 Ψ 0 | Ĥ C | Ψ 0 〉, where Ψ 0 is the ground-state wave function of the QM site. 1 The first-order perturbation describes the interaction of the protein–water–membrane classical system with the unperturbed electronic density of the QM region. In contrast, the second-order QM perturbation in the Coulomb interaction Hamiltonian Ĥ C incorporates polarization of the QM electronic cloud by the medium.…”

“…A series expansion of the electronic energy in the electric field is truncated at the second order in eqn (1). Terms of higher order can be obtained by diagonalizing the multipolar expansion Hamiltonian 6,7 H ˆ= H ˆ0 + H ˆC À lÁE s , (2) where l is the electronic dipole moment operator.…”

Long-Time Oxygen and Superoxide Localization in Arabidopsis thaliana Cryptochrome

“…Our current approach samples independently the product and reactant states, with large ranges of unsampled energy gap values (see Figure ). Enhanced sampling techniques such as umbrella sampling or metadynamics that can better sample transition-state configurations may improve the electron-transfer rate estimates. − It is also known that Marcus theory calculations can in some cases give poor estimates for the electron-transfer rates. , Several recent studies have utilized nonadiabatic QM/MM methods to better represent the electron-transfer process. ,,,− This appears to be a promising avenue to improve the fidelity of the electron-transfer model in At CRY1.…”

Determination of SWCNT biosensor for bisphosphonate–2X(X = Mg2+, Ca2+, Sr2+) delivery in bone cell through electromagnetic and thermodynamic analysis using QM/MC methods

“…Neridronic acid (C 6 H 17 NO 7 P 2 ) is in a class of bisphosphonates medications which is used to treat imperfect osteogenesis and Paget's disease of bone (Gatti et al, 2009;Varenna et al, 2013). Pamidronic acid (C 3 H 11 NO 7 P 2 ) is another N-containing BP used to prevent osteoporosis and strengthen bone in Paget's disease (Kubalek et al, 2001;Zarychanski et al, 2006). In this work, the authors have applied the methodology of hybrid quantum mechanical/molecular mechanical (QM/MM) methods which are essential keys for the investigation of biosensors.…”