Accurate Biomolecular Structures by the Nano-LEGO Approach: Pick the Bricks and Build Your Geometry

Abstract

The determination of accurate equilibrium molecular structures plays a fundamental role for understanding many physical–chemical properties of molecules, ranging from the precise evaluation of the electronic structure to the analysis of the role played by dynamical and environmental effects in tuning their overall behavior. For small semi-rigid systems in the gas phase, state-of-the-art quantum chemical computations rival the most sophisticated experimental (from, for example, high-resolution spectroscopy) results. For larger molecules, more effective computational approaches must be devised. To this end, we have further enlarged the compilation of available semi-experimental (SE) equilibrium structures, now covering the most important fragments containing H, B, C, N, O, F, P, S, and Cl atoms collected in the new SE100 database. Next, comparison with geometries optimized by methods rooted in the density functional theory showed that the already remarkable results delivered by PW6B95 and, especially, rev-DSDPBEP86 functionals can be further improved by a linear regression (LR) approach. Use of template fragments (taken from the SE100 library) together with LR estimates for the missing interfragment parameters paves the route toward accurate structures of large molecules, as witnessed by the very small deviations between computed and experimental rotational constants. The whole approach has been implemented in a user-friendly tool, termed nano-LEGO, and applied to a number of demanding case studies.

The Spectroscopic Characterization of Halogenated Pollutants through the Interplay between Theory and Experiment: Application to R1122

“…The lack of isotopic substitutions on F atoms, which prevents a reliable determination of the structural parameters involving them, can be overcome by using two strategies: the non-determinable parameters can be constrained to an accurate theoretical value or, alternatively, one can resort to the use of the predicate observations method, which uses estimates of structural parameters as additional input data [ 74 ]. In addition to being more flexible with respect to treating theoretical parameters as rigid constraints, it should lead to more precise results [ 75 , 76 ]. In the present work, this second method has been adopted with predicates for the C3−F4 and C3−F6 bond lengths and C2C3F4 and C2C3F6 angles taken from the CCSD(T)/CBS+CV gradient scheme results.…”

“…The equilibrium geometry obtained by using the large cc-pV5Z basis set is also in agreement with the SE structure, even though larger deviations than those for composite methods can be noted. A strikingly accurate equilibrium geometry is obtained by augmenting the PW6B95 and rev-DSDPBEP86 results through the nano-LEGO approach [ 76 ]. In fact, whereas for the bare functionals, differences as large as 6–7 mÅ are obtained, as can be seen in Table S1 of the Supplementary Materials (SM) , the nano-LEGO procedure lowers the deviations to 1.2 mÅ, thus reaching the same accuracy as the CCSD(T)-based composite methods but at a far lower computational cost.…”

A Computational Journey across Nitroxide Radicals: From Structure to Spectroscopic Properties and Beyond

“…It is well documented that B2 equilibrium geometries are remarkably accurate [ 32 ]; nonetheless higher level calculations performed on small model systems can provide information to correct the structures of larger molecules obtained at lower computational levels following the template molecule and/or linear regression approaches (referred to in the following as TMA and LRA, respectively) [ 13 ].…”

“…In recent years, methods rooted in the density functional theory (DFT) have emerged as the methods of choice for medium- to large-size molecular systems not amenable to the most accurate (but also prohibitively expensive) wave-function methods. In this connection, several studies have shown that double-hybrid functionals in conjunction with partially augmented triple-zeta basis sets are particularly reliable for geometrical structures, vibrational frequencies and several other spectroscopic properties [ 7 , 12 , 13 ]. On these grounds, we have performed a comprehensive study of several prototypical nitroxide radicals using as benchmarks either available experimental data or state-of-the-art QC results.…”

Toward Accurate Formation Routes of Complex Organic Molecules in the Interstellar Medium: The Paradigmatic Cases of Acrylonitrile and Cyanomethanimine

“…In this connection, the B2PLYP-D3/ maug-cc-pVTZ model (Grimme, 2006;Papajak et al, 2009) employed in our earlier studies has recently been replaced by the rev-DSD-PBEP86 functional (Santra et al, 2019) in conjunction with the jun-cc-pVTZ (Papajak et al, 2011) basis set (such a functional-basis combination is shortly denoted as rev-DSD in the following), which usually delivers improved results (with respect to the former) for transition states and non-covalent complexes without reducing the accuracy of other parameters. When more accurate geometries are sought (especially in connection with spectroscopic properties or intermolecular distances of pre-reactive complexes), more accurate quantum-chemical approaches (vide infra) or a "LEGO bricks" approach can be employed (Ceselin et al, 2021;Melli et al, 2021).…”