Electrostatically embedded molecules‐in‐molecules approach and its application to molecular clusters

Abstract

We report the application of our fragment-based quantum chemistry model MIM (Molecules-In-Molecules) with electrostatic embedding. The method is termed "EE-MIM (Electrostatically Embedded Molecules-In-Molecules)" and accounts for the missing electrostatic interactions in the subsystems resulting from fragmentation. Point charges placed at the atomic positions are used to represent the interaction of each subsystem with the rest of the molecule with minimal increase in the computational cost. We have carefully calibrated this model on a range of different sizes of clusters containing up to 57 water molecules. The fragmentation methods have been applied with the goal of reproducing the unfragmented total energy at the MP2/6-311G(d,p) level. Comparative analysis has been carried out between MIM and EE-MIM to gauge the impact of electrostatic embedding. Performance of several different parameters such as the type of charge and levels of fragmentation are analyzed for the prediction of absolute energies. The use of background charges in subsystem calculations improves the performance of both one-and two-layer MIM while it is noticeably important in the case of one-layer MIM. Embedded charges for two-layer MIM are obtained from a full system calculation at the low-level. For onelayer MIM, in the absence of a full system calculation, two different types of embedded charges, namely, Geometry dependent (GD) and geometry independent (GI) charges, are used. A self-consistent procedure is employed to obtain GD charges. We have further tested our method on challenging charged systems with stronger intermolecular interactions, namely, protonated ammonia clusters (containing up to 30 ammonia molecules). The observations are similar to water clusters with improved performance using embedded charges. Overall, the performance of NPA charges as embedded charges is found to be the best.

Landscape of In Silico Tools for Modeling Covalent Modification of Proteins: A Review on Computational Covalent Drug Discovery

“…With a bird’s-eye view, while accuracy has been a major issue for docking algorithms, speed is the major concern for QM/MM FEP-based approaches. These can be addressed by focusing on critical factors such as incorporation of QM information in docking scoring functions, intelligent implementation of the Zwanzig equation, , development of multilayered fragment-based QM methods, − and system-dependent selection of QM sizes in QM/MM models. Nonetheless, with further development in computer power and more accurate methods, CCDD is poised to become a great tool in medicinal chemistry in the near future.…”

EE-ONIOM-CT Method to Efficiently Account for the Missing Interactions in ONIOM: Energies and Analytic Gradients

“…Variational formulation and implementation of analytic derivatives of the method enable efficient MD simulations . The DSCF (double self-consistent field) form has some similarity with fragmentation methods such as FMO and EE-MIM …”

“…20 The DSCF (double self-consistent field) form has some similarity with fragmentation methods such as FMO 21 and EE-MIM. 22 The analogous methods for ONIOM (QM:QM) have not yet been fully developed. Two different methods were proposed by our group to account for the missing interactions separately, viz., ONIOM-CT 23,24 (ONIOM with Charge Transfer corrections) and ONIOM-EE 25−28 (ONIOM with electrostatic embedding) to correct for charge transfer and electrostatic interactions, respectively.…”

Benchmarking various types of partial atomic charges for classical all-atom simulations of metal–organic frameworks

“…21 However, a recent study found that no definite conclusion can be drawn on the suitability of these two charge types for capturing long-range electrostatic interactions. 24 When compared to the DDEC method, it is well known that the CM5 method can cause smaller charges in metal sulfide MS 2 and metal selenide MSe 2 solids but larger charges in other lattices. 25 Therefore, for various MOFs, pairwise comparisons among Mulliken, CM5 and DDEC charges are warranted.…”