Empirical corrections and pair interaction energies in the fragment molecular orbital method

The energy and analytic gradient are developed for FMO combined with the Hartree-Fock method augmented with three empirical corrections (HF-3c). The auxiliary basis set approach to FMO is extended to perform pair interaction energy decomposition analysis. The FMO accuracy is evaluated for several typical systems including 3 proteins. Pair interaction energies computed with different approaches in FMO are compared for a water cluster and protein-ligand complexes.Comment: Revised version accepted in Chemical Physics Letter

Ab Initio Study of Molecular Interactions in Cellulose Iα

Biomass recalcitrance, the resistance of cellulosic biomass to degradation, is due in part to the stability of the hydrogen bond network and stacking forces between the polysaccharide chains in cellulose microfibers. The fragment molecular orbital (FMO) method at the correlated Møller-Plesset second order perturbation level of theory was used on a model of the crystalline cellulose Iα core with a total of 144 glucose units. These computations show that the intersheet chain interactions are stronger than the intrasheet chain interactions for the crystalline structure, while they are more similar to each other for a relaxed structure. An FMO chain pair interaction energy decomposition analysis for both the crystal and relaxed structures reveals an intricate interplay between electrostatic, dispersion, charge transfer, and exchange repulsion effects. The role of the primary alcohol groups in stabilizing the interchain hydrogen bond network in the inner sheet of the crystal and relaxed structures of cellulose Iα, where edge effects are absent, was analyzed. The maximum attractive intrasheet interaction is observed for the GT-TG residue pair with one intrasheet hydrogen bond, suggesting that the relative orientation of the residues is as important as the hydrogen bond network in strengthening the interaction between the residues

Novel Zwitterionic Copolymers to Enhance Hydrophilicity of PVDF Membranes: A Comprehensive Computational Study

Membrane technology covers all the engineering approaches with a key growth for large-scale industrial applications, including biotechnology, biomedical applications, food industry, and water and wastewater treatment. Poly (vinylidene fluoride) (PVDF) membrane has been gained remarkable attentions in recent years due to its excellent advantages in terms of thermal stability, chemical resistance, and high mechanical strength for water treatment. Despite its outstanding advantages, the performances of PVDF membranes are substantially limited by fouling problems. In this research study, we designed novel zwitterionic (ZW)-PVDF membranes with high hydrophilicity by employing a set of comprehensive computational methods. To achieve our goal, we first investigated the interactions occurring between water molecules and the fragments of hydrophobic and hydrophilic membrane models at the molecular level using the pair interaction energy decomposition analysis (PIEDA) as part of the fragment molecular orbital (FMO) method’s framework. This research direction is critical, since a research study of the reasons behind the interactions between water molecules and membrane materials would help design ground-breaking membranes with superior hydrophilicity. The computational studies and experimental analyses of PVDF and Polyacrylonitrile (PAN) membranes were considered as the models for hydrophobic and hydrophilic membranes, respectively. Density-functional theory (DFT), based on B3LYP functional and split-valance 6-311+G (d, p) basis sets, was used in order to optimize the geometry of PAN, PVDF, and their complexes with different numbers of water molecules. Furthermore, the functional groups of membrane surfaces were experimentally evaluated through Fourier-transform infrared spectroscopy (FTIR- ATR), 13C cross polarization magic angle spinning (13C CP MAS) Solid State Nuclear magnetic resonance SSNMR, and Fourier transform Raman (FT-Raman) spectroscopies. The confocal microscopic was also employed to interrogate water transport and the interactions between fluorescence particles through the membrane matrices. The non-covalent interactions in terms of electrostatic, exchange-repulsion, and charge-transfer parameters were comprehensively investigated for the designed ZW-PVDF copolymers. The performance of ZW moieties was derived from three different anionic groups in the ZW head, specifically, carboxylate, sulfonate, and phosphate. This approach was used in addition to the inclusion of a linker between the ZW head and the PVDF backbone, such as trimethyl ammonium groups and hydroxyl group, for an improvement of PVDF hydrophilicity. The quantum chemical calculations were conducted to examine the hydration structure of moieties. The interactions between the ZW moieties, with water molecules confirmed that it depended on the charged groups in addition to the chemical functional groups between charged groups. Furthermore, the types of anionic groups, the polar functional groups between charged groups, and the hydrophilic group, as a linker between charged groups of the ZW to the PVDF polymer backbone are the key reason for membrane hydrophilicity and the membrane water uptake. The double Zwitterionic PMAL®-C8-CB-OH-SB-PVDF was designed through the addition of protonated carboxyl group on a backbone of copolymer PMAL®-C8, and the protonated nitrogen atom of the amide group. This double zwitterion showed strong electrostatic interactions between individual water molecules and the secondary ammonium and the Oxygen of carboxybetaine, compared to PMAL®-C8-OH-SB-PVDF model. Our designed hydrophilic ZW-PVDF membranes, and especially the double zwitterion membrane, are an exciting development that can be applied in a broad range of water applications

Analyzing GPCR-Ligand Interactions with the Fragment Molecular Orbital (FMO) Method

G-protein-coupled receptors (GPCRs) have enormous physiological and biomedical importance, and therefore it is not surprising that they are the targets of many prescribed drugs. Further progress in GPCR drug discovery is highly dependent on the availability of protein structural information. However, the ability of X-ray crystallography to guide the drug discovery process for GPCR targets is limited by the availability of accurate tools to explore receptor-ligand interactions. Visual inspection and molecular mechanics approaches cannot explain the full complexity of molecular interactions. Quantum mechanics (QM) approaches are often too computationally expensive to be of practical use in time-sensitive situations, but the fragment molecular orbital (FMO) method offers an excellent solution that combines accuracy, speed, and the ability to reveal key interactions that would otherwise be hard to detect. Integration of GPCR crystallography or homology modelling with FMO reveals atomistic details of the individual contributions of each residue and water molecule toward ligand binding, including an analysis of their chemical nature. Such information is essential for an efficient structure-based drug design (SBDD) process. In this chapter, we describe how to use FMO in the characterization of GPCR-ligand interactions

Characterizing Rhodopsin-Arrestin Interactions with the Fragment Molecular Orbital (FMO) Method

Arrestin binding to G protein-coupled receptors (GPCRs) plays a vital role in receptor signaling. Recently, the crystal structure of rhodopsin bound to activated visual arrestin was resolved using XFEL (X-ray free electron laser). However, even with the crystal structure in hand, our ability to understand GPCR-arrestin binding is limited by the availability of accurate tools to explore receptor-arrestin interactions. We applied fragment molecular orbital (FMO) method to explore the interactions formed between the residues of rhodopsin and arrestin. FMO enables ab initio approaches to be applied to systems that conventional quantum mechanical (QM) methods would be too compute-expensive. The FMO calculations detected 35 significant interactions involved in rhodopsin-arrestin binding formed by 25 residues of rhodopsin and 28 residues of arrestin. Two major regions of interaction were identified: at the C-terminal tail of rhodopsin (D330-S343) and where the "finger loop" (G69-T79) of arrestin directly inserts into rhodopsin active core. Out of these 35 interactions, 23 were mainly electrostatic and 12 hydrophobic in nature

Characterizing Protein-Protein Interactions with the Fragment Molecular Orbital Method

Proteins are vital components of living systems, serving as building blocks, molecular machines, enzymes, receptors, ion channels, sensors, and transporters. Protein-protein interactions (PPIs) are a key part of their function. There are more than 645,000 reported disease-relevant PPIs in the human interactome, but drugs have been developed for only 2% of these targets. The advances in PPI-focused drug discovery are highly dependent on the availability of structural data and accurate computational tools for analysis of this data. Quantum mechanical approaches are often too expensive computationally, but the fragment molecular orbital (FMO) method offers an excellent solution that combines accuracy, speed and the ability to reveal key interactions that would otherwise be hard to detect. FMO provides essential information for PPI drug discovery, namely, identification of key interactions formed between residues of two proteins, including their strength (in kcal/mol) and their chemical nature (electrostatic or hydrophobic). In this chapter, we have demonstrated how three different FMO-based approaches (pair interaction energy analysis (PIE analysis), subsystem analysis (SA) and analysis of protein residue networks (PRNs)) have been applied to study PPI in three protein-protein complexes

Mapping Enzymatic Catalysis using the Effective Fragment Molecular Orbital Method: Towards all ab initio Biochemistry

We extend the Effective Fragment Molecular Orbital (EFMO) method to the frozen domain approach where only the geometry of an active part is optimized, while the many-body polarization effects are considered for the whole system. The new approach efficiently mapped out the entire reaction path of chorismate mutase in less than four days using 80 cores on 20 nodes, where the whole system containing 2398 atoms is treated in the ab initio fashion without using any force fields. The reaction path is constructed automatically with the only assumption of defining the reaction coordinate a priori. We determine the reaction barrier of chorismate mutase to be $18.3\pm 3.5$ kcal mol$^{-1}$ for MP2/cc-pVDZ and $19.3\pm 3.6$ for MP2/cc-pVTZ in an ONIOM approach using EFMO-RHF/6-31G(d) for the high and low layers, respectively.Comment: SI not attache

Cellulose and cellobiose: adventures of a wandering organic chemist in theoretical chemistry

Single-point energies resulting from the rotations of free -OH groups in the central residue of a cellulose Iα fragment consisting of nine cellotriose chains were obtained using restricted Hartree-Fock (RHF) with the 6-31G(d,p) basis set, density functional theory with the B3LYP functional using the 6-31G(d,p), and the fragment molecular orbital (FMO) method at the FMO2 method with second order perturbation theory (MP2) and the 6-31G(d) basis set. Potential energy curves calculated using these three methods are in excellent agreement with each other for the dihedral angles corresponding to energy maxima and minima. The calculated relative energies using the DFT/B3LYP and FMO2/MP2 levels of theory differ from each other by an average of 0.5 kcal/mol, 0.5 kcal/mol, and 1.1 kcal/mol when each of the -OH groups attached to the C2, C3, and C6 atoms, respectively, were rotated. The use of the pair interaction energy decomposition analysis (PIEDA) with the pair interaction energies from the dimer part of the FMO2 calculations also allowed the identification of the glucose residues most significantly involved in contributing to the rotational energy barriers. Intrachain and interchain interactions (those occurring between residues found in the same cellulose sheet) were seen to be stronger than intersheet interactions (occurring between residues found in different cellulose sheets) in contributing to the relative energy changes due to the rotations of free -OH groups in cellulose. Restricted Hartree-Fock (RHF) and density functional theory (DFT) methods were used to determine the energies involved in the acid-catalyzed hydrolysis of cellobiose in the gas phase. A stepwise mechanism for the reaction was used to determine the different species involved. The initial step was protonation of a cellobiose molecule with a hydronium ion, which was followed by removal of a molecule of water to produce protonated cellobiose. Dissociation of the protonated cellobiose followed to produce a β-D-glucose molecule and a glucosyl cation. The cation in turn was hydrated to produce an α-D-glucose molecule. The energy change for the dissociation step was determined to be +36.8 kcal/mol using density functional theory with the B3LYP functional and 6-311+G(d,p) basis set. The calculated value is similar to those obtained from experimental data and from a recent solution phase Car-Parrinello molecular dynamics calculation

Multiscale Modeling for Host-Guest Chemistry of Dendrimers in Solution

Dendrimers have been widely used as nanostructured carriers for guest species in a variety of applications in medicine, catalysis, and environmental remediation. Theory and simulation methods are an important complement to experimental approaches that are designed to develop a fundamental understanding about how dendrimers interact with guest molecules. This review focuses on computational studies aimed at providing a better understanding of the relevant physicochemical parameters at play in the binding and release mechanisms between polyamidoamine (PAMAM) dendrimers and guest species. We highlight recent contributions that model supramolecular dendrimer-guest complexes over the temporal and spatial scales spanned by simulation methods ranging from all-atom molecular dynamics to statistical field theory. The role of solvent effects on dendrimer-guest interactions and the importance of relating model parameters across multiple scales is discussed

Studi Perbandingan Metode Fragment Molecular Orbital (FMO) dengan Mekanika Kuantum Konvensional Serta Pengaruh Solvasi Air Implisit dan Eksplisit Pada Sistem yang Tersusun dari Natrium, Emas, dan Sitrat

Studying biomolecule-gold nanoparticle (AuNP) interactions is an important aspect in order to explore potential applications of AuNP in diagnostic and therapeutic fields. Biomolecule-AuNP interactions involve electrostatic interactions and charge transfer from nucleophilic functional groups to AuNP, thereby investigating biomolecule-AuNP interactions requires quantum mechanics (QM). Fragment molecular orbital (FMO) is QM approach with faster computation time than conventional QM, especially for systems composed of many atoms. Biomolecule-AuNP interaction can be investigated through pair interaction energy decomposition analysis (PIEDA) obtained from FMO calculations. The purpose of this study to investigate the agreement between FMO calculations and conventional QM in systems consist of Na+ , Au, citrate3- , and H2O; and to investigate effect of implicit and explicit water solvation on FMO calculations. Model compounds used are [Na(H2O)4] + , [Na(H2O)6] + *, [Na(H2O)6] + , [Na(citrate)2] 5- , [Au(H2O)2], and [Au(citrate)]3- . Although FMO underestimate total energy (Etotal) of [Na(H2O)4] + , [Na(H2O)6] + *, [Na(H2O)6] + , and [Na(citrate)2] 5- , prediction of ΔE reaction with that Etotal in agreement with conventional QM. FMO also predicts partial charges in agreement with conventional QM. Calculations in implicit water reduce the excessive EES interaction due to not taking into account the electrostatic interactions of solute fragments with solvent, especially in interactions between positively and negatively charged fragments. Solvation in implicit water can also cause substantial differences in EEX and E(CT+mix) compared to a vacuum state, thereby it has different decomposition pattern. Calculations in explicit water cause charge of solute fragments not interger like its formal charge due to charge transfer between water and solute fragments. Explicit solvent calculations more realistic for studying biomolecule-AuNP interactions because explicitly include solvent effect on charge distribution