Linear Scaling Quantum Mechanical Method Research Articles

Unusual shift in the visible absorption spectrum of an active ctenophore photoprotein elucidated by time-dependent density functional theory.

Active hydromedusan and ctenophore Ca2+-regulated photoproteins form complexes consisting of apoprotein and strongly non-covalently bound 2-hydroperoxycoelenterazine (an oxygenated intermediate of coelenterazine). Whereas the absorption maximum of hydromedusan photoproteins is at 460-470nm, ctenophore photoproteins absorb at 437nm. Finding out a physical reason for this blue shift is the main objective of this work, and, to achieve it, the whole structure of the protein-substrate complex was optimized using a linear scaling quantum-mechanical method. Electronic excitations pertinent to the spectra of the 2-hydroperoxy adduct of coelenterazine were simulated with time-dependent density functional theory. The dihedral angle of 60°of the 6-(p-hydroxy)-phenyl group relative to the imidazopyrazinone core of 2-hydroperoxycoelenterazine molecule was found to be the key factor determining the absorption of ctenophore photoproteins at 437nm. The residues relevant to binding of the substrate and its adopting the particular rotation were also identified.

Electrostatic polarization is critical for the strong binding in streptavidin‐biotin system

The origin of strong affinity of biotin and its analogs binding to (strept)avidin is still the subject of an ongoing controversy. In this work, thermodynamic integration is carried out to study of the difference of binding free energies between biotin and iminobiotin to streptavidin. Three atomic charge schemes are implemented and compared. One is the traditional AMBER charge, and the other two, termed the polarized protein-specific charge, are based on a linear scaling quantum mechanical method and a continuous solvation model and have polarization effect partially or fully included. The result indicates that when nonpolarized AMBER force field is applied, the result is much underestimated. When electronic polarization is gradually included, the difference of binding affinity increases along with it. Using the linear-response approximation to eliminate the error in self-charging process, the corrected binding affinity agrees well with the experimental observation. This study is direct evidence indicating that polarization effect is critical for the strong binding in streptavidin-biotin system.

Structure of Graphene, and Mechanical and Bonding Characteristics of Single Wall Carbon Nanotube by Linear Scaling Quantum Mechanical Method

Using a linear scaling self-consistent-charge density functional tight binding (SCC-DFTB) and an ab initio Dmol method, the bonding characteristics and Young's modulus of (10, 0) and (10,10) single-walled carbon nanotubes are calculated. The structure of a graphene is also calculated. It is found that the C-C and C-H bond length, their distribution characteristics on the tube, and Young's modulus of the tube by linear scaling SCC-DFTB are identical to those by ab initio, while the computing cost by the linear scaling SCC-DFTB is reduced by more than 30 times as compared with that by the Dmol for the (10,0) and (10,10) tubes By computing the structure of a graphene it is also found that the linear scaling SCCDFTB is reliable and time-saving.

Computational alanine scanning with linear scaling semiempirical quantum mechanical methods

Alanine scanning is a powerful experimental tool for understanding the key interactions in protein-protein interfaces. Linear scaling semiempirical quantum mechanical calculations are now sufficiently fast and robust to allow meaningful calculations on large systems such as proteins, RNA and DNA. In particular, they have proven useful in understanding protein-ligand interactions. Here we ask the question: can these linear scaling quantum mechanical methods developed for protein-ligand scoring be useful for computational alanine scanning? To answer this question, we assembled 15 protein-protein complexes with available crystal structures and sufficient alanine scanning data. In all, the data set contains Delta Delta Gs for 400 single point alanine mutations of these 15 complexes. We show that with only one adjusted parameter the quantum mechanics-based methods outperform both buried accessible surface area and a potential of mean force and compare favorably to a variety of published empirical methods. Finally, we closely examined the outliers in the data set and discuss some of the challenges that arise from this examination.

QUANTUM CALCULATION OF PROTEIN SOLVATION AND PROTEIN–LIGAND BINDING FREE ENERGY FOR HIV-1 PROTEASE/WATER COMPLEX

HIV-1 protease (PR) is a primary target for anti-HIV therapeutics. A well conserved water molecule, denoted as W301, is found in almost all the crystallographic structures of PR/inhibitor complexes and it plays an important role in PR/inhibitor binding. As the PR/inhibitor interaction depends on the ionization state of the cleavage site which contains an aspartyl dyad (Asp25/Asp25′), the determination of the protonation states of aspartyl dyad in PR may be essential for drug design. In this study, a linear scaling quantum mechanical method, molecular fragmentation with conjugate caps (MFCC), is used for interaction study of PR/ABT-538 and W301 at four different monoprotonation states of the Asp25/Asp25′. Combined method of MFCC and conductor-like polarizable continuum model (CPCM) is applied in binding affinity calculation for four minimum energy structures which are extracted from four different molecular dynamics trajectories corresponding to four different monoprotonation states of Asp25/Asp25′. Our result is in good agreement with previous result obtained by FEP/TI method, showing that the conserved W301 contributes significantly to the binding free energy of PR/ABT-538 complex and different protonation states of Asp25/Asp25′ have significant impact on the binding free energy contribution from W301.

A quantum mechanical approach to ligand binding — Calculation of ligand–protein binding affinities for stromelysin-1 (MMP-3) inhibitors

Linear-scaling quantum mechanical method was applied to calculate binding affinities of six stromelysin-1 (MMP-3) inhibitors with two different zinc binding groups (ZBGs). The entire protein and ligand–protein complexes were calculated using PM5 Hamiltonian, which enables the treatment of metal ion coordination, bond forming/breaking, and proton/charge transfers associated with the ligand binding process by the self-consistent field method. The calculated binding energies reproduce the binding-affinity trend observed experimentally.

Effect of ending surface on energy and Young's modulus of single-walled carbon nanotubes studied using linear scaling quantum mechanical method

Abstract By using a linear scaling self-consistent charge, density functional tight-binding (SCC-DFTB) method and an ab intio Dmol3 calculation, the energy and Young's modulus as a function of tube length for (10, 0) single-walled carbon nanotubes (SWCNTs) are investigated. It was found that with increasing the length of SWCNTs the Young's modulus increases rapidly, then, there is a slow increase, which ultimately approaches a constant value after the length is increased to ~20 nm, whereas a reversed variation tendency was found for the average energy of atoms in SWCNTs with a change of the tube length. We found that the characters of the length-dependent energy and Young's modulus stem from the changed Py-DOS of atoms in the ending region of the tube. Here one simple formula is proposed for quantitatively explaining the length-dependent energy and modulus.

Linear scaling molecular orbital calculations of biological systems using the semiempirical divide and conquer method

A “linear-scaling revolution” is occurring in quantum chemistry. This development is allowing for the first time the routine examination of large molecular assembles (e.g., proteins and DNA in water) using electronic structure methods. One of these approaches is the divide and conquer method and, in this article, we review the implementation of this approach for semiempirical Hamiltonians. This is then followed by brief reviews of three application areas. First, we will discuss the charge distribution of biological molecules in solution as described by quantum mechanics. In particular, the role polarization and charge transfer plays in affecting the charge distribution of proteins will be discussed. Next, we will examine the energetic consequences of charge transfer and polarization on biomolecular solvation. The final section will describe the computation of solvation free energies using a combined divide and conquer/Poisson–Boltzmann approach. The application of linear scaling quantum mechanical methods to biology is only just beginning, but the future is very bright, and it is our opinion that quantum mechanics will have a profound influence on our understanding of biological systems in the coming years. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 1494–1504, 2000