Transfer learning of hyperparameters for fast construction of anisotropic GPR models: design and application to the machine-learned force field FFLUX.

The polarisable machine-learned force field FFLUX requires pre-trained anisotropic Gaussian process regression (GPR) models of atomic energies and multipole moments to propagate unbiased molecular dynamics simulations. The outcome of FFLUX simulations is highly dependent on the predictive accuracy of the underlying models whose training entails determining the optimal set of model hyperparameters. Unfortunately, traditional direct learning (DL) procedures do not scale well on this task, especially when the hyperparameter search is initiated from a (set of) random guess solution(s).

Incorporating Noncovalent Interactions in Transfer Learning Gaussian Process Regression Models for Molecular Simulations.

FFLUX is a quantum chemical topology-based multipolar force field that uses Gaussian process regression machine learning models to predict atomic energies and multipole moments on the fly for fast and accurate molecular dynamics simulations. These models have previously been trained on monomers, meaning that many-body effects, for example, intermolecular charge transfer, are missed in simulations. Moreover, dispersion and repulsion have been modeled using Lennard-Jones potentials, necessitating careful parametrization.

Unraveling the crystal structure, stability and drug likeness of 1,3,4-oxadiazole derivatives against Myelofibrosis: a combined experimental and computational investigation.

Herein, we report the synthesis and characterization of novel 1,3,4-oxadiazole derivatives, 2-methoxybenzyl 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate () (), and methoxybenzyl 5-(3-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate () obtained through desulfurative cyclization reaction. The compound was crystallized, and its crystal structure was elucidated using single-crystal X-ray diffraction technique. The Hirshfeld surface analysis was carried out to analyze, visualize and globally appreciate the weak interactions involved in crystal packing.

An Unsupervised Machine Learning Approach for the Automatic Construction of Local Chemical Descriptors.

Condensing the many physical variables defining a chemical system into a fixed-size array poses a significant challenge in the development of chemical Machine Learning (ML). Atom Centered Symmetry Functions (ACSFs) offer an intuitive featurization approach by means of a tedious and labor-intensive selection of tunable parameters. In this work, we implement an unsupervised ML strategy relying on a Gaussian Mixture Model (GMM) to automatically optimize the ACSF parameters.

Bond dissociation energies of ethyl valerate and tripropionin.

Context: Due to the expected decrease in the availability of conventional oils, numerous studies are currently underway to find complementary sources of energy. Among the explored avenue is that of biofuels. Ethyl valerate (ETV) and tripropionin (TPP) are two biofuels whose thermal decomposition has not received the attention it deserves.

An Integrated Analysis of Mechanistic Insights into Biomolecular Interactions and Molecular Dynamics of Bio-Inspired Cu(II) and Zn(II) Complexes towards DNA/BSA/SARS-CoV-2 3CL by Molecular Docking-Based Virtual Screening and FRET Detection.

Novel constructed bioactive mixed-ligand complexes () [Cu(L)(phen)] and () [Zn(L)(phen)] {where, L = 2-(4-morpholinobenzylideneamino)phenol), phen = 1,10-phenanthroline} have been structurally analysed by various analytical and spectroscopic techniques, including, magnetic moments, thermogravimetric analysis, and X-ray crystallography. Various analytical and spectral measurements assigned showed that all complexes appear to have an octahedral geometry. Agar gel electrophoresis's output demonstrated that the Cu(II) complex () had efficient deoxyribonucleic cleavage and complex () demonstrated the partial cleavage accomplished with an oxidation agent, which generates spreadable OH through the Fenton type mechanism.

Comprehensive Assessment of Biomolecular Interactions of Morpholine-Based Mixed Ligand Cu(II) and Zn(II) Complexes of 2,2'-Bipyridine as Potential Anticancer and SARS-CoV-2 Agents: A Synergistic Experimental and Structure-Based Virtual Screening.

A new class of pharmacologically active mixed-ligand complexes (-) [M(L) (bpy)], where  = 2-(4-morpholinobenzylideneamino)phenol), bpy = 2,2'-bipyridine, M = Cu (), and Zn (), were assigned an octahedral geometry by analytical and spectral measurements. Gel electrophoresis showed that complex () demonstrated the complete DNA cleavage mediated by HO. The overall DNA-binding constants observed from UV-vis, fluorometric, hydrodynamic, and electrochemical titrations were in the following sequence: () > () > (), which suggests that the complexes might intercalate DNA, a possibility that is further supported by the biothermodynamic characteristics.

A multiscale ONIOM study of the buckminsterfullerene (C) Diels-Alder reaction: from model design to reaction path analysis.

The hybrid ONIOM (Our own N-layered Integrated molecular Orbital and molecular Mechanics) formalism is employed to investigate the Diels-Alder reaction of the buckminsterfullerene C. Our computations suggest that the ONIOM2(M06-2X/6-31G(d): SVWN/STO-3G) model, enclosing both the diene and the pyracyclene fragment of C60 in the higher-layer, provides a reasonable trade-off between accuracy and computational cost as it comes to predicting reaction energetics. Moreover, the frontier molecular orbital (FMO) theory and activation strain model (ASM) are jointly relied on to rationalize the effect of -OH and -CN substituents on the activation barrier of this reaction.

In silico Drug Repurposing of Anticancer Drug 5-FU and Analogues Against SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics Simulation, Pharmacokinetics and Chemical Reactivity Studies.

Background: Since the last COVID-19 outbreak, several approaches have been given a try to quickly tackle this global calamity. One of the well-established strategies is the drug repurposing, which consists in finding new therapeutic uses for approved drugs. Following the same paradigm, we report in the present study, an investigation of the potential inhibitory activity of 5-FU and nineteen of its analogues against the SARS-CoV-2 main protease (3CLpro).

Spectro-electrochemical, fluorometric and biothermodynamic evaluation of pharmacologically active morpholine scaffold single crystal ligand and its metal(II) complexes: A comparative study on in-vitro and in-silico screening towards DNA/BSA/SARS-CoV-19.

A novel series of metal(II) complexes (1-5) [M(L)]{Where M = Cu (1), Co (2), Mn (3), Ni (4) and Zn (5)} constructed from 2-(4-morpholinobenzylideneamino)phenol Schiff base ligand (HL) in a 1:2 M ratio and the spectral and analytical results put forward square planar geometry. Spectro-electrochemical, hydrodynamic, gel electrophoresis, and DNA binding/cleavage results for all the compounds demonstrate that complex (1) had excellent DNA binding/cleavage properties compared to other compounds. The observation also suggests that test compounds could intercalate with DNA, and the biothermodynamic property more strongly supports the stabilizing of the double helix DNA with the complexes.

AMADAR: a python-based package for large scale prediction of Diels-Alder transition state geometries and IRC path analysis.

Predicting transition state geometries is one of the most challenging tasks in computational chemistry, which often requires expert-based knowledge and permanent human intervention. This short communication reports technical details and preliminary results of a python-based tool (AMADAR) designed to generate any Diels-Alder (DA) transition state geometry (TS) and analyze determined IRC paths in a (quasi-)automated fashion, given the product SMILES. Two modules of the package are devoted to performing, from IRC paths, reaction force analyses (RFA) and atomic (fragment) decompositions of the reaction force F and reaction force constant [Formula: see text].

New Insights into the (A)Synchronicity of Diels-Alder Reactions: A Theoretical Study Based on the Reaction Force Analysis and Atomic Resolution of Energy Derivatives.

In the present manuscript, we report new insights into the concept of (a)synchronicity in Diels-Alder (DA) reactions in the framework of the reaction force analysis in conjunction with natural population calculations and the atomic resolution of energy derivatives along the intrinsic reaction coordinate (IRC) path. Our findings suggest that the DA reaction transitions from a preferentially concerted mechanism to a stepwise one in a 0.10 Å window of synchronicity indices ranging from 0.

Structure, stability and bonding of the leapfrog B .

Two new structural motifs of the B clusters are constructed by use of the leapfrog transformation. The resulting leapfrog B has either a bowl shape with a square vacancy or a quasi-planar 2D close-packed triangular boron sheet. The neutral and ionic forms of the latter are found to be more stable than their homologous leapfrog bowl clusters, with the exception of the dicationic B .

Interplay between σ Holes, Anion···H-C, and Cation-π Interactions in Dibromo[2,2]paracyclophane Complexes.

Theoretical calculations were performed to investigate the interplay between σ-hole, anion-HC and cation-π interactions in the complexes of dibromo[2,2]paracyclophane (DBr[2,2]PCP) with alkali (Li, Na, K), alkaline earth metal cations (Be, Mg, and Ca), and halogen anions (F, Cl, and Br) using the wave function (MP2) and density functional theory (M06-2X and B3LYP) methods with the 6-311++G(d,p) basis set. The study reveals that DBr[2,2]PCP behaves as amphoteric molecule with a predominance of basic character. It prefers to interact with hard cations and hard anions such as Be and F through cation-π and anion···HC interactions, respectively.