How well do semiempirical QM methods describe the structure of proteins?

Semiempirical quantum-mechanical (QM) computational methods are an increasingly popular tool for the study of biomolecular systems. They were, however, developed and tested mostly on small model molecules. In this work, we explore one topic fundamental to these applications: the ability of the methods to describe the structure of proteins. In a set of 19 proteins for which a crystal structure with very high resolution is available, we analyze the properties of the protein geometries optimized using several semiempirical QM methods including PM6-D3H4, PM7, and GFN2-xTB. Some of the methods provide a very good description of the general structural features of the protein, yielding results better than or comparable to the AMBER ff03 force field. However, PM7 and PM6-D3H4 optimizations introduce artificial close contacts in the structure, which is partially remediated by reparameterization.

DFTB+, a software package for efficient approximate density functional theory based atomistic simulations.

DFTB+ is a versatile community developed open source software package offering fast and efficient methods for carrying out atomistic quantum mechanical simulations. By implementing various methods approximating density functional theory (DFT), such as the density functional based tight binding (DFTB) and the extended tight binding method, it enables simulations of large systems and long timescales with reasonable accuracy while being considerably faster for typical simulations than the respective ab initio methods. Based on the DFTB framework, it additionally offers approximated versions of various DFT extensions including hybrid functionals, time dependent formalism for treating excited systems, electron transport using non-equilibrium Green's functions, and many more. DFTB+ can be used as a user-friendly standalone application in addition to being embedded into other software packages as a library or acting as a calculation-server accessed by socket communication. We give an overview of the recently developed capabilities of the DFTB+ code, demonstrating with a few use case examples, discuss the strengths and weaknesses of the various features, and also discuss on-going developments and possible future perspectives.

Testing Semiempirical Quantum Mechanical Methods on a Data Set of Interaction Energies Mapping Repulsive Contacts in Organic Molecules.

Semiempirical quantum mechanical (QM) methods with corrections for noncovalent interactions provide a favorable combination of accuracy and computational efficiency that makes them a useful tool for a study of large molecular systems. It was, however, noted that the accuracy of these methods deteriorates at intermolecular distances shorter than equilibrium. In this work, we explore this issue systematically using a newly developed data set of benchmark interaction energies named R160×6. This data set maps repulsive contacts in organic molecules, and it consists of 160 model complexes for which six points along the dissociation curve are provided. Testing a wide range of semiempirical QM methods against the CCSD(T)/CBS benchmark revealed that most methods, and all the dispersion-corrected ones, underestimate the repulsion systematically. The worst cases are usually hydrogen-hydrogen contacts. The best results were obtained with PM6-D3H4 and DFTB3-D3H4, as these methods already contain a correction for the H-H repulsion, but the errors are still about twice as large as in equilibrium geometries.

Optical method for measuring thermal accommodation coefficients using a whispering-gallery microresonator.

A novel optical method has been developed for the measurement of thermal accommodation coefficients in the temperature-jump regime. The temperature dependence of the resonant frequency of a fused-silica microresonator's whispering-gallery mode is used to measure the rate at which the microresonator comes into thermal equilibrium with the ambient gas. The thermal relaxation time is related to the thermal conductivity of the gas under some simplifying assumptions and measuring this time as a function of gas pressure determines the thermal accommodation coefficient. Using a low-power tunable diode laser of wavelength around 1570 nm to probe a microsphere's whispering-gallery mode through tapered-fiber coupling, we have measured the accommodation coefficients of air, helium, and nitrogen on fused silica at room temperature. In addition, by applying thin-film coatings to the microsphere's surface, we have demonstrated that accommodation coefficients can be measured for various gases on a wide range of modified surfaces using this method.

Benzene Dimer: High-Level Wave Function and Density Functional Theory Calculations.

High-level OVOS (optimized virtual orbital space) CCSD(T) interaction energy calculations (up to the aug-cc-pVQZ basis set) and various extrapolations toward the complete basis set (CBS) limit are presented for the most important structures on the benzene dimer potential energy surface. The geometries of these structures were obtained via an all-coordinate gradient geometry optimization using the DFT-D/BLYP method, covering the empirical dispersion correction fitted exclusively for this system. The fit was carried out against two estimated CCSD(T)/CBS potential energy curves corresponding to the distance variation between two benzene rings for the parallel-displaced (PD) and T-shaped (T) structures. The effect of the connected quadruple excitations on the interaction energy was estimated using the CCSD(TQf) method in a 6-31G*(0.25) basis set, destabilizing the T and T-shaped tilted (TT) structures by ≈0.02 kcal/mol and the PD structure by ≈0.04 kcal/mol. Our best CCSD(T)/CBS results show, within the error bars of the applied methodology, that the energetically lowest-lying structure is the TT structure, which is nearly 0.1 kcal/mol more stable than the almost isoenergetic PD and T structures. The specifically parametrized DFT-D/BLYP method leads to a correct energy ordering of the structures, with the errors being smaller by 0.2 kcal/mol with respect to the most accurate CCSD(T) values.

Locking a microsphere whispering-gallery mode to a laser.

We have locked a whispering-gallery resonance of a fused-silica microsphere to a frequency-scanning laser. The resonance frequency is modulated by axial compression of the microsphere, and phase-sensitive detection of the fiber-coupled optical throughput is used for locking. Using a laser wavelength of either 1570 nm or 830 nm, we demonstrate a locked tracking range exceeding 30 GHz for a microsphere of 120 GHz free spectral range. This performance has been enabled by an improved compression tuner design that allows coarse tuning over 1 THz and piezoelectric tuning over 80 GHz. Compression modulation rates of up to 13 kHz have also been achieved with this tuner.

Disseminated intravascular coagulation associated with toxic epidermal necrolysis (Lyell's syndrome).

Evidence of disseminated intravascular coagulation was recorded in eight patients with toxic epidermal necrolysis (TEN)--Lyell's syndrome. Patients were treated with low doses of heparin in combination with the usual treatment of TEN, i.e. maintenance of fluid and electrolyte balance, systemic corticosteroids, antibiotics and aseptic dressings, in the Intensive Care Unit environment. It is suggested that the alteration of haemostasis and inter-related biological systems, such as activation of components of complement, kinins and immunoglobulins, may affect the outcome of TEN.